New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Temperature-Controlled Chain Dynamics in Polyimide Doped with CoCl2 Probed Using Dynamic Mechanical Analysis.

Cobalt(II) chloride (CoCl2) being in the vicinity of polyimide chains entails modifications in terms of the molecular dynamics, which are mainly governed by the possible presence of amic acid residual groups, by the transition-metal-type characteristics of cobalt and by the CoCl2 content. Polyimide was synthesized using poly(amic acid) according to the reaction of 2,2'-bis(3,4-dicarboxylphenyl)hexafluoropropane dianhydride (6FDA) with 3,3'-dimethyl-4,4'-diaminodiphenylmethane (MMDA) in N,N-dimethylacetamide. CoCl2 was added before the thermal imidization of the poly(amic acid). An experimental approach was designed to establish the interaction between the polyimide and CoCl2 and whether the interaction depends on the quantity of the salt. Evidence for the existence of residual amic acid groups was obtained using second derivative Fourier Transform Infrared Spectroscopy (FTIR) and with the help of 2D correlation spectroscopy (2D-COS). Moreover, FTIR, along with X-ray photoelectron spectroscopy (XPS), revealed the interaction between the polymer and CoCl2, primarily in the form of Co(II)-N coordinated bonds. Nevertheless, the coordination of cobalt with suitable atoms from the amic acid groups is not precluded. The results of dynamic mechanical analysis (DMA) featured a specific relaxation assigned to the presence of CoCl2 in the polymeric film and demonstrated that its (non)reinforcing effect depends on its content in the polyimide.

Comprehensive Elemental Profiling of Romanian Honey: Exploring Regional Variance, Honey Types, and Analyzed Metals for Sustainable Apicultural and Environmental Practices.

We investigated the mineral concentrations of 61 honey samples from eight Romanian regions, employing advanced techniques to assess 30 chemical elements. Potassium emerged as the dominant element, showcasing significant variations across geographical locations. Essential minerals like calcium, magnesium, sodium, and manganese maintained consistent levels, while zinc, copper, and chromium were present in smaller proportions. Critically, lead and cadmium levels exceeded established safety limits in some samples, suggesting potential environmental contamination. Additionally, elevated levels of lithium, strontium, nickel, and aluminum were detected, hinting at possible atmospheric pollution. These findings highlight the importance of regional analysis, as mineral content varied significantly between locations. Furthermore, correlation analysis revealed interdependencies among elements, suggesting shared environmental influences. Advanced statistical techniques like hierarchical clustering and principal component analysis effectively captured the impact of geographical origin on honey composition. These insights contribute valuable information for future efforts in honey quality control, traceability systems, and regulatory measures. By providing valuable insights into environmental influences on honey composition, this study informs future research endeavors and paves the way for the development of robust regulatory measures to ensure honey safety for consumers.

Development of Solid Lipid Nanoparticles for Controlled Amiodarone Delivery.

In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients-Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone.

Scurvy complicated with Capnocytophaga sputigena sepsis as a possible cause of death of king Saint-Louis of France (1270 AD).

The cause of death of Saint-Louis is not known, but recent findings indicated that he presented scurvy and inflammatory jaw disease, which has been associated with infection by oral commensals. Here, we have the exceptional opportunity to analyze the relics of the viscera of King Saint-Louis. A 4.3 g sample from the viscera relics of King Saint-Louis conserved in Versailles' cathedral was subjected to radiocarbon dating, electronic and optic microscopy, and elementary, palynological, molecular, proteomics and microbiological analyses including specific PCR and v3v4 16 S rRNA gene amplification prior to large-scale sequencing using an Illumina MiSeq instrument. The measured radiocarbon age was Cal 1290 CE-1400, which was compatible with that of the viscera of St Louis viscera, considering the addition of lime, incense and vegetables within the human organs. Elemental and palynological analyses confirmed a medieval embalming process. Proteomics analysis identified mainly human muscle and blood proteins. Specific PCR for plague, amoebiasis, shigellosis and typhoid fever was negative. C. sputigena was identified as the main pathogenic species representing 10.8 % of all microbial sequences. In contrast, C. sputigena was found in only 0.001 % of samples sequenced in our center, and the 23 positive human samples showed a dramatically lower abundance (0.02-2.6 %). In the literature, human infections with C. sputigena included odontitis, dental abscess, sinusitis, thoracic infections and bacteremia, particularly in immunocompromised patients with oral and dental diseases consistent with recent analysis of King Saint-Louis' jaw. C. sputigena, a commensal of the mouth that is potentially pathogenic and responsible for fatal bacteremia, may have been the cause of the king's death.

The Influence of Phytosociological Cultivation and Fertilization on Polyphenolic Content of Menthae and Melissae folium and Evaluation of Antioxidant Properties through In Vitro and In Silico Methods.

Since medicinal plants are widely used in treating various diseases, phytoconstituents enrichment strategies are of high interest for plant growers. First of all, we investigated the impact of phytosociological cultivation on polyphenolic content (total flavonoids-TFL, and total polyphenols-TPC) of peppermint (Mentha piperita L.) and lemon balm (Melissa officinalis L.) leaves, using spectrophotometric methods. Secondly, the influence of chemical (NPK) and organic (BIO) fertilization on polyphenolic content and plant material quality was also assessed. Dry extracts were obtained from harvested leaves using hydroethanolic extraction solvents for further qualitative and quantitative assessment of phytoconstituents by FT-ICR MS and UHPLC-MS. Furthermore, the antioxidant activity of leaf extracts was determined in vitro using DPPH, ABTS and FRAP methods. Molecular docking simulations were employed to further evaluate the antioxidant potential of obtained extracts, predicting the interactions of identified phytochemicals with sirtuins. The concentration of polyphenols was higher in the plant material harvested from the phytosociological culture. Moreover, the use of BIO fertilizer led to the biosynthesis of a higher content of polyphenols. Higher amounts of phytochemicals, such as caffeic acid, were determined in extracts obtained from phytosociological crops. The antioxidant activity was dependent on polyphenols concentration, more potent inhibition values being observed for the extracts obtained from the phytosociological batches. Molecular docking studies and MM/PBSA calculations revealed that the obtained extracts have the potential to directly activate sirtuins 1, 5 and 6 through several polyphenolic compounds, such as rosmarinic acid, thus complementing the free radical scavenging activity with the potential stimulation of endogenous antioxidant defense mechanisms. In conclusion, growing medicinal plants in phytosociological cultures treated with biofertilizers can have a positive impact on plant material quality, concentration in active constituents and biological activity.

The Polyphenolic Profile and Antioxidant Activity of Five Vegetal Extracts with Hepatoprotective Potential.

Oxidative stress is among the major triggers for many important human functional disorders, which often lead to various metabolic or tissue diseases. The aim of the study is to obtain five standardized vegetal extracts (Cynarae extractum-CE, Rosmarini extractum-RE, Taraxaci extractum-TE, Cichorii extractum-CHE, and Agrimoniae extractum-AE) that contain active principles with an essential role in protecting liver cells against free radicals and quantify their antioxidant actions. The compounds of therapeutic interest from the analyzed extracts were identified and quantified using the UHPLC-HRMS/MS technique. Thus, the resulting identified compounds were 28 compounds in CE, 48 compounds in RE, 39 compounds in TE, 43 compounds in CHE, and 31 compounds in AE. These compounds belong to the class of flavonoids, isoflavones, phenolic acids and dicarboxylic acids, depsides, diterpenes, triterpenes, sesquiterpenes, proanthocyanidins, or coumarin derivatives. From the major polyphenolic compounds quantified in all the extracts analyzed by UHPLC-HRMS/MS, considerable amounts have been found for chlorogenic acid (619.8 µg/g extract for TE-2032.4 µg/g extract for AE), rutoside (105.1 µg/g extract for RE-1724.7 µg/g extract for AE), kaempferol (243 µg/g extract for CHE-2028.4 µg/g extract for CE), and for naringenin (383 µg/g extract for CHE-1375.8 µg/g extract for AE). The quantitative chemical analysis showed the highest content of total phenolic acids for AE (24.1528 ± 1.1936 g chlorogenic acid/100 g dry extract), the highest concentration of flavones for RE (6.0847 ± 0.3025 g rutoside/100 g dry extract), and the richest extract in total polyphenols with 31.7017 ± 1.2211 g tannic acid equivalent/100 g dry extract for AE. Several methods (DPPH, ABTS, and FRAP) have been used to determine the in vitro total antioxidant activity of the extracts to evaluate their free radical scavenging ability, influenced by the identified compounds. As a result, the correlation between the content of the polyphenolic compounds and the antioxidant effect of the extracts has been demonstrated. Statistically significant differences were found when comparing the antiradical capacity within the study groups. Although all the analyzed extracts showed good IC50 values, which may explain their antihepatotoxic effects, the highest antioxidant activity was obtained for Agrimoniae extractum (IC50ABTS = 0.0147 mg/mL) and the lowest antioxidant activity was obtained for Cynarae extractum (IC50ABTS = 0.1588 mg/mL). Furthermore, the hepatoprotective potential was evaluated in silico by predicting the interactions between the determined phytochemicals and key molecular targets relevant to liver disease pathophysiology. Finally, the evaluation of the pharmacognostic and phytochemical properties of the studied extracts validates their use as adjuvants in phytotherapy, as they reduce oxidative stress and toxin accumulation and thus exert a hepatoprotective effect at the cellular level.

Gold/Pentablock Terpolymer Hybrid Multifunctional Nanocarriers for Controlled Delivery of Tamoxifen: Effect of Nanostructure on Release Kinetics.

Here, we describe the preparation and characterization of organic/inorganic hybrid polymer multifunctional nanocarriers. Novel nanocomposites of gold nanoparticles using pH-responsive coordination pentablock terpolymers of poly(ε-caprolactone)-b-poly(ethylene oxide)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide)-b-poly(ε-caprolactone), bearing or not bearing partially quaternized vinylpyridine moieties, were studied. The template morphology of the coordination pentablock terpolymer at physiological pH ranges from crew-cut to multicompartmentalized micelles which can be tuned by chemical modification of the central block. Additionally, the presence of 2VP groups allows the coordination of gold ions, which can be reduced in situ to construct gold@polymer nanohybrids. Furthermore, the possibility of tuning the gold distribution in the micelles, through partial quaternization of the central P2VP block, was also investigated. Various morphological gold colloidal nanoparticles such as gold@core-corona nanoparticles and gold@core-gold@corona nanoparticles were synthesized on the corresponding template of the pentablock terpolymer, first by coordination with gold ions, followed by reduction with NaBH4. The pentablock and gold@pentablock nanoparticles could sparingly accommodate a water-soluble drug, Tamoxifen (TAX), in their hydrophobic micellar cores. The nanostructure of the nanocarrier remarkably affects the TAX delivery kinetics. Importantly, the hybrid gold@polymer nanoparticles showed prolonged release profiles for the guest molecule, relative to the corresponding bare amphiphilic pentablock polymeric micelles. These Gold@pentablock terpolymer hybrid nanoparticles could act as a multifunctional theranostic nanoplatform, integrating sustainable pH-controlled drug delivery, diagnostic function and photothermal therapy.

Gelatin Reinforced with CNCs as Nanocomposite Matrix for Trichoderma harzianum KUEN 1585 Spores in Seed Coatings.

Increasing interest on sustainable agriculture has led to the development of new materials which can be used as seed coating agents. In this study, a new material was developed based on gelatin film reinforced with cellulose nanocrystals (CNC) which was further used as nanocomposite matrix for Trichoderma harzianum KUEN 1585 spores. The nanocomposite films were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), showing the formation of new hydrogen bonds between the components with a good compatibility between them. Measurements of water contact angles and tests of water vapor sorption and swelling degree revealed an improvement in the water vapor absorption properties of the films as a result of their reinforcement with CNC. Furthermore, by adding the Trichoderma harzianum KUEN 1585 spp. in the seed coating material, the germination percentage, speed of germination and roots length of the corn seeds improved. The polymeric coating did not inhibit the growth of T. harzianum KUEN 1585, with this material being a good candidate in modern agriculture.

Interplay Between Endocrine Disruptors and Immunity: Implications for Diseases of Autoreactive Etiology.

The sex-bias of disease susceptibility has remained a puzzling aspect of several autoimmune conditions, including post-infection viral autoimmunity. In the last half of the twentieth century, the incidence rate of female-biased autoimmunity has steadily increased independent of medical advances. This has suggested a role for environmental factors, such as endocrine disrupting chemicals, which have been described to interfere with endocrine signaling. Endocrine involvement in the proper function of innate and adaptive immunity has also been defined, however, these two areas have rarely been reviewed in correlation. In addition, studies addressing the effects of endocrine disruptors have reported findings resulting from a broad range of exposure doses, schedules and models. This experimental heterogeneity adds confusion and may mislead the translation of findings to human health. Our work will normalize results across experiments and provide a necessary summary relevant to human exposure. Through a novel approach, we describe how different categories of ubiquitously used environmental endocrine disruptors interfere with immune relevant endocrine signaling and contribute to autoimmunity. We hope this review will guide identification of mechanisms and concentration-dependent EDC effects important not only for the sex-bias of autoimmunity, but also for other conditions of immune dysfunction, including post-infection autoreactivity such as may arise following severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, Herpes Simplex virus.

Teleworking-An Economic and Social Impact during COVID-19 Pandemic: A Data Mining Analysis.

The health crisis generated by the COVID-19 pandemic has induced, among other things, an increase in the importance of remote work or teleworking (TL) in the current period. The objective of this research is to identify the economic and social impact of telework in changing the behavior of employees in Romania. The research was conducted approximately one year after the onset of the pandemic until the beginning of the vaccination period in Romania. The research proposed includes three main directions of analysis of the extracted data, which are related to telework efficiency, this being considered one of the most important indicators for a company. In order to obtain conclusive results, we used a mixed methodology, combining results obtained through a survey based on a self-administered electronic questionnaire, with a data mining analysis. Detailed analysis of the groups identified based on work efficiency allowed us to highlight the most common employee profiles. This analysis was doubled by a second classification experiment, which provided us a more detailed analysis of the groups identified based on job satisfaction and highlighted the most common employee profiles. The expansion of telework in various economic areas is a result of adaptation to the new economic and social conditions caused by the COVID-19 pandemic.

Effect of Cellulose Nanocrystals Nanofiller on the Structure and Sorption Properties of Carboxymethyl Cellulose-Glycerol-Cellulose Nanocrystals Nanocomposite Systems.

Biobased materials present a great interest due to their properties and biodegradability. Cellulose nanocrystals (CNC) nanofiller, in various amounts, was incorporated into a carboxymethyl cellulose (CMC)-glycerol (G) matrix in order to obtain nanocomposite systems with improved properties. The effect of the nanofiller on the structural features was investigated by Fourier transform infrared (FT-IR) spectroscopy, principal component analysis (PCA), two-dimensional correlation spectroscopy (2D-COS), and X-ray diffraction, while the sorption properties were evaluated by water vapor isotherms using the gravimetric method coupled with infrared spectroscopy. We observed the presence of the interactions taking place between the CMC-G and CNC involving the hydroxyl and carboxylate groups, which decreased the number of water sorption sites. Following this, the moisture content in the nanocomposite films decreased with the increase in the amount of CNC. Moreover, the bands associated to water molecules presented different wavenumber values separated for CMC-G and CNC components.

CD11c+ T-bet+ B Cells Require IL-21 and IFN-γ from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-bet.

CD11c+ T-bet+ B cells generated during ehrlichial infection require CD4+ T cell help and IL-21 signaling for their development, but the exact T cell subset required had not been known. In this study, we show in a mouse model of Ehrlichia muris that type 1 T follicular helper (TFH1) cells provide help to CD11c+ T-bet+ B cells via the dual secretion of IL-21 and IFN-γ in a CD40/CD40L-dependent manner. TFH1 cell help was delivered in two phases: IFN-γ signals were provided early in infection, whereas CD40/CD40L help was provided late in infection. In contrast to T-bet+ T cells, T-bet+ B cells did not develop in the absence of B cell-intrinsic Bcl-6 but were generated in the absence of T-bet. T-bet-deficient memory B cells were largely indistinguishable from their wild-type counterparts, although they no longer underwent switching to IgG2c. These data suggest that a primary function of T-bet in B cells during ehrlichial infection is to promote appropriate class switching, not lineage specification. Thus, CD11c+ memory B cells develop normally without T-bet but require Bcl-6 and specialized help from dual cytokine-producing TFH1 cells.

Synthesis and characterization of κ-carrageenan bio-nanocomposite films reinforced with bentonite nanoclay.

Due to ecological reason, in the last period there is an increased interest for changing the synthetic based materials with biodegradable ones. In this study, we prepared bio-nanocomposite formulations based on κ-Carrageenan (κ) and bentonite nanoclay (BT) with different component concentrations (0% BT, 5% BT, 10% BT and 15% BT respectively) and investigated their structural features, with focus on the interactions, sorption properties, and how the combination between them influences these properties. By infrared spectroscopy was identified that in the blending process hydrogen bonds and/or electrostatic interactions may have occurred between BT and κ. The water uptake and water sorption ability decreased with the increasing of the BT content in the formulations, from about 12% for κ to 9% for κ-BT 85:15% and from about 128% for κ to 121% for κ-BT 85:15%, respectively. Water adsorption can significantly decrease if the reinforcement materials are homogenusly dispersed in the matrix. The increase of the BT content induced also a decrease of the water contact angle at the surface from 76o for κ to 27o for κ-BT 85:15%.

TNF-α Contributes to Lymphoid Tissue Disorganization and Germinal Center B Cell Suppression during Intracellular Bacterial Infection.

Bacterial, parasitic, and viral infections are well-known causes of lymphoid tissue disorganization, although the factors, both host and/or pathogen derived, that mediate these changes are largely unknown. Ehrlichia muris infection in mice causes a loss of germinal center (GC) B cells that is accompanied by the generation of extrafollicular T-bet+ CD11c+ plasmablasts and IgM memory B cells. We addressed a possible role for TNF-α in this process because this cytokine has been shown to regulate GC development. Ablation of TNF-α during infection resulted in an 8-fold expansion of GL7+ CD38lo CD95+ GC B cells, and a 2.5- and 5-fold expansion of CD138+ plasmablasts and T-bet+ memory cells, respectively. These changes were accompanied by a reduction in splenomegaly, more organized T and B cell zones, and an improved response to Ag challenge. CXCL13, the ligand for CXCR5, was detected at 6-fold higher levels following infection but was much reduced following TNF-α ablation, suggesting that CXCL13 dysregulation also contributes to loss of lymphoid tissue organization. T follicular helper cells, which also underwent expansion in infected TNF-α--deficient mice, may also have contributed to the expansion of T-bet+ B cells, as the latter are known to require T cell help. Our findings contrast with previously described roles for TNF-α in GCs and reveal how host-pathogen interactions can induce profound changes in cytokine and chemokine production that can alter lymphoid tissue organization, GC B cell development, and extrafollicular T-bet+ B cell generation.

Structural and sorption properties of bio-nanocomposite films based on κ-carrageenan and cellulose nanocrystals.

There is an increased interest on changing the synthetic based materials to biodegradable ones, especially with natural polymers, polysaccharides or proteins. In this research we prepared bio-nanocomposite formulations with different component concentrations and investigated their structural features, with focus on the interactions, sorption properties, and how the combination between them influences these properties. By infrared spectroscopy, principal component analysis (PCA) and two-dimensional correlation spectroscopy (2DCOS) was identified that in the blending process are involved the -SO4 and C(4)-O-S groups of ß-d-galactose, CO groups, (O=S=O) of carrageenan and -OH and CO groups from CNCs. The water uptake and water sorption properties decrease with increasing the CNCs content in the formulations from about 15% for κ to 10% for κC15 and from about 128% for κ to 115% for κC15, respectively. The increase of the CNCs content induced an increase of the water contact angle from 47° for κ to 90° for κC15, indicating once again the involvement of the free hydroxyl groups in the hydrogen bonded interactions.

Structural and morphological evaluation of CNC reinforced PVA/Starch biodegradable films.

Nanocomposite films containing cellulose nanocrystals (CNC), as the reinforcing phase, and poly(vinyl alcohol) (PVA)/starch (S) blend, as the matrix, were prepared by solution casting technique. For the preparation, 5, 10, 15 wt% CNC suspension were incorporated in blends containing 90 wt% PVA/10 wt% S, 75 wt% PVA/25 wt% S and 50 wt% PVA/50 wt% S. Structural evaluation was done by Fourier transform infrared spectrometry and X-ray diffraction, and the morphological aspects by atomic force microscopy. Infrared spectroscopy evidenced the presence of H-bond interactions between the PVA and S and between PVA/S blend and CNC, and also variation in the conformational rearrangement, while the X-ray diffraction showed that the crystallite size and the degree of crystallinity were strongly affected by blending of PVA with S and also by the incorporation of CNC in the nanocomposite films. The surface roughness of studied samples increased with the increasing of S and filler content.

Paclitaxel controlled delivery using a pH-responsive functional-AuNP/block-copolymer vesicular nanocarrier composite system.

Paclitaxel (PTX)-loaded gold nanoparticles functionalized with mercaptooctanoic acid (MOA) and folic acid (FA) (AuMOA-FA) were encapsulated within pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-PEO) vesicles with the aim to develop a more selective injectable nano-formulation for PTX, lacking the side effects of the conventional PTX delivery system. The size of the resulting composite vesicles was lower than 200 nm, i.e. it is suitable for tumor targeting applications taking advantage of the enhanced permeability and retention (EPR) effect. The vesicles did not aggregate in the presence of high electrolyte concentrations, indicating the colloidal stability of the vesicles. The vesicles did not leak their AuMOA-FA or PTX content at physiological pH of 7.4. However, AuMOA-FA and PTX release were significantly accelerated at acidic pHs resembling tumor environment and acidic intracellular compartments. PTX release from the vesicles at acidic pH apparently follows AuMOA-FA release from the vesicles. Flow cytometry measurements and confocal laser scanning microscopy images showed that the vesicles could enter A549 cancer cells in culture and that cellular uptake increased with time. Blank vesicles did not exhibit cytotoxicity and did not induce apoptosis in A549 cancer cells. The PTX currying vesicles exhibited comparable or a little higher cytotoxicity than free PTX. Both the PTX currying vesicles and free PTX induced A549 cells apoptosis, however the vesicle-encapsulated PTX induced a higher percentage of late apoptotic cells than free PTX.

Structural changes of wood during hydro-thermal and thermal treatments evaluated through NIR spectroscopy and principal component analysis.

Spruce wood samples were subjected to different conditions of thermal and hydro-thermal treatment by varying the temperature, relative humidity and period of exposure. The obtained treated samples were evaluated using near infrared spectroscopy (NIR), principal component analysis (PCA) and hierarchical cluster analysis (HCA) in order to evidence the structural changes which may occur during the applied treatment conditions. Following this, modification in all wood components were observed, modifications which were dependent on the temperature, amount of relative humidity and also the treatment time. Therefore, higher variations were evidenced for samples treated at higher temperatures and for longer periods. At the same time, the increase in the amount of water vapours in the medium induced a reduced rate of side chains and condensation reactions occurring in the wood structure. Further, by PCA and HCA was possible to discriminate the modifications in the wood samples according to treatment time and amount of relative humidity.

Usefulness of ultrastructure studies for the estimation of the postmortem interval. A systematic review.

Establishing the postmortem interval (PMI) is vital in legal medicine as it allows to retrospectively estimate the hour of death, which is essential for the police as a starting point for their inquiries (especially in violent deaths). Ultrastructure studies aimed specifically to detect autolytic changes are scarcely identified in the scientific literature. Moreover, they are performed in a variety of conditions (different temperatures, species, in vitro ÷ in situ, and so on), making the results difficult to interpret for legal medicine purposes. The main aim of this review is to determine the potential usefulness of ultrastructure studies for the estimation of the postmortem interval and to provide a summary of relevant scientific literature in the area, which might be useful as a starting point for more specific and detailed studies in the field. We performed a search on the ISI Thomson Web of Knowledge database using a series of predefined keywords; the articles fulfilling the inclusion criteria were systematically analyzed to identify ultrastructure changes associated with autolysis. Our investigation revealed 20 relevant articles, which detailed ultrastructure changes in the brain, heart, liver, pancreas, kidney, bone, sweat glands, thyroid, skeletal muscle, cartilage and sweat glands. For each organ, we arranged systematically postmortem ultrastructure changes that were described by various authors. Ultrastructure changes appear early and may be useful in determining the time since death in the early postmortem interval. However, most studies published in this area followed methodologies that could not allow a proper reproducibility in forensic circumstances. Therefore, before using ultrastructure for estimating the PMI in practical environments, further studies are needed. They should be performed ideally on human samples, obtained at regular intervals after death, at variable, decreasing temperatures.