Hydrolytic Breakdown Research Articles

Materials based on biodegradable polymers chitosan/gelatin: a review of potential applications.

Increased mass manufacturing and the pervasive use of plastics in many facets of daily life have had detrimental effects on the environment. As a result, these worries heighten the possibility of climate change due to the carbon dioxide emissions from burning conventional, non-biodegradable polymers. Accordingly, biodegradable gelatin and chitosan polymers are being created as a sustainable substitute for non-biodegradable polymeric materials in various applications. Chitosan is the only naturally occurring cationic alkaline polysaccharide, a well-known edible polymer derived from chitin. The biological activities of chitosan, such as its antioxidant, anticancer, and antimicrobial qualities, have recently piqued the interest of researchers. Similarly, gelatin is a naturally occurring polymer derived from the hydrolytic breakdown of collagen protein and offers various medicinal advantages owing to its unique amino acid composition. In this review, we present an overview of recent studies focusing on applying chitosan and gelatin polymers in various fields. These include using gelatin and chitosan as food packaging, antioxidants and antimicrobial properties, properties encapsulating biologically active substances, tissue engineering, microencapsulation technology, water treatment, and drug delivery. This review emphasizes the significance of investigating sustainable options for non-biodegradable plastics. It showcases the diverse uses of gelatin and chitosan polymers in tackling environmental issues and driving progress across different industries.

Chitosan in biomedicine: A comprehensive review of recent developments

A naturally occurring biopolymer, chitosan has found widespread application in the fields of biomedical research and healthcare enhancement. Through a thorough analysis of recent research findings and technological advancements, this review seeks to provide a comprehensive overview of the latest developments and potential uses of chitosan in the field of biomedicine. Microbe cells' anionic lipopolysaccharides and surface proteins interact with the polycationic composition, releasing intracellular components and resulting in cell death. The degree of antimicrobial activity is highly dependent on the particular type of microbe being targeted. Chitosan is highly susceptible to enzymatic hydrolytic breakdown pathways in the human body, especially when lysozymes are involved. Moreover, adding chitosan derivatives to mice's diet improved their health by increasing their enzymatic activity, which is related to its scavenging properties and shows anti-microbial activity. Furthermore, the assessment of sutures manufactured from this substance emphasizes their noteworthy input to the field of modern wound care.

Contaminants of emerging concern: Silylation procedures, evaluation of the stability of silyl derivatives and associated measurement uncertainty

Analyte range of gas chromatography–mass spectrometry (GC–MS), widely used in environmental analysis, can be significantly broadened by derivatization. Silyl derivatives have improved volatility and thermal stability, chromatographic and mass spectrometric behaviors, and thus detection, structural elucidation and quantification. However, silylation use is often hindered by the stability of generated derivatives and the need to optimize silylation conditions. In this study, we optimized the derivatization conditions for 70 selected contaminants of emerging concern (CEC) using chemometrics approaches. N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA), N, O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and BSTFA + 1 % trimethylchlorosilane (TMCS) were investigated, among which the latter gave the best yield. CEC were grouped in three derivatization protocols: 60 °C/45 min, 70 °C/90 min, and 70 °C/45 min. The short- and long-term stability of the CEC-trimethylsilyl (TMS) derivatives, i.e. for 28 days and up to 20 weeks were examined in a solvent and artificial wastewater (AWW) extract at 25 °C, 4 °C and − 18 °C, and during repeated five freeze-thaw (F/T) cycles, at two concentration levels: 100 μg/L and 1000 μg/L. Except for TMS derivatives of shikimic acid (SHA), quinic acid (QA) and sulfanilamide (SFA), the remaining derivatized compounds were stable in solvent (EtAc) for 28 days. In AWW extract, TMS derivatives of citric acid (CA), 17β-estradiol (E2), estriol (E3) and 17α-ethinyl estradiol (EE2) were unstable at 25 °C and 4 °C. Within up to 20 weeks, only the TMS derivatives of CA, meso-erythritol (ERY) and bisphenol BP (BPBP) were unstable. The most significant hydrolytic breakdown was observed during repeated F/T cycles. After three cycles, ≤ 20 % of the initial concentration of six and nine CEC-TMS derivatives had degraded in solvent and AWW extracts, respectively. According to the deep statistical comparison (DSC) approach, the most prominent degradation was observed for TMS derivatives of E2, CA, 9-hydroxyfluorene (9-HF), estrone (E1) and trans-3′-hydroxycotinine (T3HC) in solvent; E2, CA, 9-HF, E3 and E1 in AWW extracts and ERY, E2, CA, 9-HF and E1 in both matrices. Finally, the sample concentration of CEC accounted for most of the measurement uncertainty (MU).Based on our findings, we recommend the derivatized samples to be stored at −18 °C for up to 20 weeks to ensure the stability of their TMS derivatives. Sample freezing and thawing of not more than twice is allowed to maintain ≥80 % of the initial CEC-TMS concentration.

Factors influencing the recovery of organic nitrogen from fresh human urine dosed with organic/inorganic acids and concentrated by evaporation in ambient conditions

To feed the world without transgressing regional and planetary boundaries for nitrogen and phosphorus, one promising strategy is to return nutrients present in domestic wastewater to farmland. This study tested a novel approach for producing bio-based solid fertilisers by concentrating source-separated human urine through acidification and dehydration. Thermodynamic simulations and laboratory experiments were conducted to evaluate changes in chemistry of real fresh urine dosed and dehydrated using two different organic and inorganic acids. The results showed that an acid dose of 1.36 g H2SO4 L−1, 2.86 g H3PO4 L−1, 2.53 g C2H2O4·2H2O L−1 and 5.9 g C6H8O7 L−1 was sufficient to maintain pH ≤3.0 and prevent enzymatic ureolysis in urine during dehydration. Unlike alkaline dehydration using Ca(OH)2 where calcite formation limits the nutrient content of fertiliser products (e.g. <15 % nitrogen), there is greater value proposition in acid dehydration of urine, as the products contain 17.9–21.2 % nitrogen, 1.1–3.6 % phosphorus, 4.2–5.6 % potassium and 15.4–19.4 % carbon. While the treatment recovered all phosphorus, recovery of nitrogen in the solid products was 74 % (±4 %). Follow-up experiments revealed that hydrolytic breakdown of urea to ammonia, chemically or enzymatically, was not the reason for the nitrogen losses. Instead, we posit that urea breaks down to ammonium cyanate, which then reacts with amino and sulfhydryl groups of amino acids excreted in urine. Overall, the organic acids evaluated in this study are promising for decentralised urine treatment, as they are naturally present in food and therefore already excreted in human urine.

Urea-Formaldehyde Resin Removal in Medium-Density Fiberboards by Steam Explosion: Developing Nondestructive Analytical Tools

The cascading recycling of wood waste is currently a hot topic. Medium-density fiberboard (MDF) is a material whose consumption has been increasing worldwide for several decades. However, current wood waste treatment processes do not allow for efficient recycling. The potential of steam explosion (SE) treatment was investigated for stripping off the urea-formaldehyde (UF) resin and producing clean fibers from MDF. Hot liquid water during the hydrothermal stage and water expansion during the decompression stage of SE provoked the (1) hydrolytic breakdown of UF and removal of >80% of resin from the fibers and (2) efficient defibration of MDF producing ≈67% of fibers with similar morphological features when compared with MDF fibers. Near infrared spectroscopy (NIRS), nitrogen quantification, and confocal laser scanning microscopy/scanning electron microscopy-wavelength dispersive spectroscopy were used to evaluate the SE effect on UF removal from MDF fibers. The sample clusters obtained by principal component analysis of NIRS spectra were correlated with the nitrogen content and processing conditions used. This work brings versatile solutions based on hydrothermal treatments, namely SE, for diverse low environmental impact and valorization routes of MDF waste. We showed that MDF processing treatment must be chosen wisely according to the future valorization of the MDF targeted.

Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs

Pulmonary administration of biodegradable polymeric formulation is beneficial in the treatment of various respiratory diseases. For respiratory delivery, the polymer must be non-toxic, biodegradable, biocompatible, and stable. Poly D, L-lactic-co-glycolic acid (PLGA) is a widely used polymer for inhalable formulations because of its attractive mechanical and processing characteristics which give great opportunities to pharmaceutical industries to formulate novel inhalable products. PLGA has many pharmaceutical applications and its biocompatible nature produces non-toxic degradation products. The degradation of PLGA takes place through the non-enzymatic hydrolytic breakdown of ester bonds to produce free lactic acid and glycolic acid. The biodegradation products of PLGA are eliminated in the form of carbon dioxide (CO2) and water (H2O) by the Krebs cycle. The biocompatible properties of PLGA are investigated in various in vivo and in vitro studies. The high structural integrity of PLGA particles provides better stability, excellent drug loading, and sustained drug release. This review provides detailed information about PLGA as an inhalable grade polymer, its synthesis, advantages, physicochemical properties, biodegradability, and biocompatible characteristics. The important formulation aspects that must be considered during the manufacturing of inhalable PLGA formulations and the toxicity of PLGA in the lungs are also discussed in this paper. Additionally, a thorough overview is given on the application of PLGA as a particulate carrier in the treatment of major respiratory diseases, such as cystic fibrosis, lung cancer, tuberculosis, asthma, and pulmonary hypertension.

Design, synthesis, anti-acetylcholinesterase evaluation and molecular modelling studies of novel coumarin-chalcone hybrids

The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer’s disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman’s method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL. Communicated by Ramaswamy H. Sarma

Biodegradation of poly(butylene succinate) in soil laboratory incubations assessed by stable carbon isotope labelling

Using biodegradable instead of conventional plastics in agricultural applications promises to help overcome plastic pollution of agricultural soils. However, analytical limitations impede our understanding of plastic biodegradation in soils. Utilizing stable carbon isotope (13C-)labelled poly(butylene succinate) (PBS), a synthetic polyester, we herein present an analytical approach to continuously quantify PBS mineralization to 13CO2 during soil incubations and, thereafter, to determine non-mineralized PBS-derived 13C remaining in the soil. We demonstrate extensive PBS mineralization (65 % of added 13C) and a closed mass balance on PBS−13C over 425 days of incubation. Extraction of residual PBS from soils combined with kinetic modeling of the biodegradation data and results from monomer (i.e., butanediol and succinate) mineralization experiments suggest that PBS hydrolytic breakdown controlled the overall PBS biodegradation rate. Beyond PBS biodegradation in soil, the presented methodology is broadly applicable to investigate biodegradation of other biodegradable polymers in various receiving environments.

Zeolites and Biochar Modulate Olive Fruit and Oil Polyphenolic Profile.

Soil degradation processes and climate change threaten the sustainability of Mediterranean rainfed olive orchards, with repercussions on crop yield and quality of olives, olive oil and olive by-products. Using soil amendments can enhance soil fertility for sustained environmental quality and plant performance. For two years, we evaluated, under rainfed conditions, the effects of a fertilizer compound (FC) and its combination with zeolites (ZL) and biochar (BC) amendments on soil moisture, yield, fruit and oil polyphenols and quality indices. The polyphenolic composition was strongly influenced by treatments, although no effects were observed on crop yield. ZL improved soil moisture (average increase of 26.3% compared to FC), fruit fatty acid composition (increase of 12.4% in oleic/linoleic ratio in 2018) and oil quality, BC enhanced the concentrations of polyphenols with high nutritional value (average annual increase of 25.6, 84.8 and 11.6% for 3,4-dihydroxyphenylglycol, oleuropein and rutin, respectively). In contrast, olive oil from FC fruits showed the poorest quality, with oxidation and hydrolytic breakdown signals. The applied soil amendments appear to be a promising sustainable strategy to implement in olive rainfed orchards.

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs) and cardiovascular diseases (CVDs) are illnesses that affect the nervous system and heart, all of which are vital to the human body. To maintain health of the human body, vegetable diets serve as a preventive approach and particularly Brassica vegetables have been associated with lower risks of chronic diseases, especially NDDs and CVDs. Interestingly, glucosinolates (GLs) and isothiocyanates (ITCs) are phytochemicals that are mostly found in the Cruciferae family and they have been largely documented as antioxidants contributing to both cardio- and neuroprotective effects. The hydrolytic breakdown of GLs into ITCs such as sulforaphane (SFN), phenylethyl ITC (PEITC), moringin (MG), erucin (ER), and allyl ITC (AITC) has been recognized to exert significant effects with regards to cardio- and neuroprotection. From past in vivo and/or in vitro studies, those phytochemicals have displayed the ability to mitigate the adverse effects of reactive oxidation species (ROS), inflammation, and apoptosis, which are the primary causes of CVDs and NDDs. This review focuses on the protective effects of those GL-derived ITCs, featuring their beneficial effects and the mechanisms behind those effects in CVDs and NDDs.

Predicting the hydrolytic breakdown rates of organophosphorus chemical warfare agent simulants using association constants derived from hydrogen bonded complex formation events

ABSTRACT Organophosphorus (OP) chemical warfare agents (CWAs) represent an ongoing global threat, through either purposeful environmental release or the need to dispose of historic stockpiles. This presents a need for the development of novel decontamination technologies. Due to the toxic nature and legal limitations placed on OP CWAs, the use of appropriate OP simulants that mimic the reactivity but not the toxicity of the agents themselves is vital to decontamination studies. Herein, we show that association constants derived from non-specific hydrogen bonded complexation events may be used as parameters within models to predict simulant reactivity. We also discuss the limitations that should be placed on such data.

Biomass utilization and production of biofuels from carbon neutral materials.

The availability of organic matters in vast quantities from the agricultural/industrial practices has long been a significant environmental challenge. These wastes have created global issues in increasing the levels of BOD or COD in water as well as in soil or air segments. Such wastes can be converted into bioenergy using a specific conversion platform in conjunction with the appropriate utilization of the methods such as anaerobic digestion, secondary waste treatment, or efficient hydrolytic breakdown as these can promote bioenergy production to mitigate the environmental issues. By the proper utilization of waste organics and by adopting innovative approaches, one can develop bioenergy processes to meet the energy needs of the society. Waste organic matters from plant origins or other agro-sources, biopolymers, or complex organic matters (cellulose, hemicelluloses, non-consumable starches or proteins) can be used as cheap raw carbon resources to produce biofuels or biogases to fulfill the ever increasing energy demands. Attempts have been made for bioenergy production by biosynthesizing, methanol, n-butanol, ethanol, algal biodiesel, and biohydrogen using different types of organic matters via biotechnological/chemical routes to meet the world's energy need by producing least amount of toxic gases (reduction up to 20-70% in concentration) in order to promote sustainable green environmental growth. This review emphasizes on the nature of available wastes, different strategies for its breakdown or hydrolysis, efficient microbial systems. Some representative examples of biomasses source that are used for bioenergy production by providing critical information are discussed. Furthermore, bioenergy production from the plant-based organic matters and environmental issues are also discussed. Advanced biofuels from the organic matters are discussed with efficient microbial and chemical processes for the promotion of biofuel production from the utilization of plant biomasses.

Anti-Herpes simplex virus (HSV-1) activity and antioxidant capacity of carrageenan-rich enzymatic extracts from Solieria filiformis (Gigartinales, Rhodophyta)

Solieria filiformis has been reported to have molecules with various biological activities. In this study we used environmentally friendly extraction methods, such as enzyme-assisted extraction (EAE), as a first step to obtain bioactive compounds from this species. Five combinations of protease (PRO) and carbohydrase (AMG) were utilized (1:0, 0:1, 2:1, 1:1, 1:2 PRO:AMG) to obtain Water Soluble Enzymatic Hydrolysates (WSEHs). Extraction yields, biochemical and structural characterization, as well as in vitro activity against Herpes simplex virus type 1 (HSV-1) and antioxidant capacities were determined. All PRO:AMG combinations significantly improved yields. EAE yielded heterogeneous extracts rich in iota-carrageenan and phenols, as confirmed by FTIR spectra. The highest antiherpetic activity (EC50 4.5 ± 0.4 μg mL−1) was found in the WSEHs obtained under 2:1 PRO:AMG. At this combination high antioxidant capacity was also obtained for ABTS (2,2′-Azino-Bis-3-ethylbenzoThiazoline-6-Sulfonic acid) radical scavenging activity and Ferric Reducing Antioxidant Power (FRAP). These could probably play a synergistic role associated to the strong antiviral activity obtained. These results suggest that 2:1 PRO:AMG could be effective in promoting the hydrolytic breakdown of high MW polysaccharides, contributing to the improvement of WSEHs bioactivity. Although Solieria filiformis WSEHs showed promising results, further research, including separation and purification techniques are needed.

Inactivation of CES1 Blocks Prostaglandin D2 Glyceryl Ester Catabolism in Monocytes/Macrophages and Enhances Its Anti-inflammatory Effects, Whereas the Pro-inflammatory Effects of Prostaglandin E2 Glyceryl Ester Are Attenuated.

Human monocytic cells in blood have important roles in host defense and express the enzyme carboxylesterase 1 (CES1). This metabolic serine hydrolase plays a critical role in the metabolism of many molecules, including lipid mediators called prostaglandin glyceryl esters (PG-Gs), which are formed during cyclooxygenase-mediated oxygenation of the endocannabinoid 2-arachidonoylglycerol. Some PG-Gs have been shown to exhibit anti-inflammatory effects; however, they are unstable compounds, and their hydrolytic breakdown generates pro-inflammatory prostaglandins. We hypothesized that by blocking the ability of CES1 to hydrolyze PG-Gs in monocytes/macrophages, the beneficial effects of anti-inflammatory prostaglandin D2-glyceryl ester (PGD2-G) could be augmented. The goals of this study were to determine whether PGD2-G is catabolized by CES1, evaluate the degree to which this metabolism is blocked by small-molecule inhibitors, and assess the immunomodulatory effects of PGD2-G in macrophages. A human monocytic cell line (THP-1 cells) was pretreated with increasing concentrations of known small-molecule inhibitors that block CES1 activity [chlorpyrifos oxon (CPO), WWL229, or WWL113], followed by incubation with PGD2-G (10 μM). Organic solvent extracts of the treated cells were analyzed by liquid chromatography with tandem mass spectrometry to assess levels of the hydrolysis product PGD2. Further, THP-1 monocytes with normal CES1 expression (control cells) and “knocked-down” CES1 expression (CES1KD cells) were employed to confirm CES1’s role in PGD2-G catabolism. We found that CES1 has a prominent role in PGD2-G hydrolysis in this cell line, accounting for about 50% of its hydrolytic metabolism, and that PGD2-G could be stabilized by the inclusion of CES1 inhibitors. The inhibitor potency followed the rank order: CPO > WWL113 > WWL229. THP-1 macrophages co-treated with WWL113 and PGD2-G prior to stimulation with lipopolysaccharide exhibited a more pronounced attenuation of pro-inflammatory cytokine levels (interleukin-6 and TNFα) than by PGD2-G treatment alone. In contrast, prostaglandin E2-glyceryl ester (PGE2-G) had opposite effects compared to those of PGD2-G, which appeared to be dependent on the hydrolysis of PGE2-G to PGE2. These results suggest that the anti-inflammatory effects induced by PGD2-G can be further augmented by inactivating CES1 activity with specific small-molecule inhibitors, while pro-inflammatory effects of PGE2-G are attenuated. Furthermore, PGD2-G (and/or its downstream metabolites) was shown to activate the lipid-sensing receptor PPARγ, resulting in altered “alternative macrophage activation” response to the Th2 cytokine interleukin-4. These findings suggest that inhibition of CES1 and other enzymes that regulate the levels of pro-resolving mediators such as PGD2-G in specific cellular niches might be a novel anti-inflammatory approach.

Effect of polydopamine incorporated dentin adhesives on bond durability

Inspired by mussel-adhesion phenomenon in wet environment, polydopamine (PDA) was tried in recent research reports to improve the dentin adhesive interface with better strength and durability. The aim of this study was to comparatively evaluate the effect of PDA incorporated dentin adhesive systems and conventional adhesive systems on degree of conversion (DC), resin dentin bond strength (SBS), durability and MMP inhibition activity. In this study, PDA was incorporated in total-etch adhesive system (TE) and self-etch adhesive systems (SE) and degree of conversion (DC%) was evaluated using Fourier transform infrared spectroscopy. Dentin slabs obtained from 160 non-carious human premolars were divided into the following: Group 1, TE; Group 2, PDA incorporated TE adhesive (TEP); Group 3, SE; Group 4, PDA incorporated SE adhesive (SEP) and bonding procedures were performed. Samples were stored for either 24 h or 6 months, after which shear bond strength and resin dentin interface was evaluated using universal testing machine and confocal laser scanning microscopy (CLSM), respectively. The zymographic assay was performed on protein extracts obtained from dentin powder treated with each of the adhesives or with or without PDA followed by functional activity assay for MMP-2 and -9. Statistical analysis was done with two-way analysis of variance and Student t-test at significance level as p < 0.05. There was statistically no significant difference in the DC% between PDA incorporated adhesives and control. No significant reduction in SBS was observed in TEP and SEP in pre- and post-aging while CLSM showed better penetration depth of resin and lesser degradation of hybrid layer on aging. Significantly lesser MMP activity was seen in PDA incorporated adhesives qualitatively and quantitatively on zymographic and functional MMP activity assay respectively. HIGHLIGHTS Catechol moieties present in polydopamine provide anti-collagenolytic activity, MMP inhibitory activity and enhances wet adhesion. Polydopamine incorporated dentin bonding systems attempts to provide stable resin dentin bond with increased bond durability. It can inhibit both proteolytic and hydrolytic breakdown of resin–dentin bond degradation.

Build orientation dependent microstructure in polymer laser sintering: Relationship to part performance and evolution with aging

Laser sintering (LS) is widely used to produce functional polymeric parts; however, the resulting parts are often limited by their porous structure, and performance of the part may be strongly anisotropic. Relating the structural features of parts to build process conditions or powder feedstock has been explored previously. In contrast, little is known regarding how the unique internal structures of LS parts evolve and relate to their performance later in their life cycle, for example, after use in a real-world operating environment. Here, a tightly controlled LS build process and measurement campaign by standard X-ray computed tomography (XCT), supported by high-resolution synchrotron XCT, was used to benchmark the internal microstructure (e.g. porosity) as a function of four different build orientations in printed polyamide-12 (PA-12) parts. The initial performance of the parts after printing was characterized by tensile testing and dynamic mechanical analysis (DMA). Arrays of PA-12 parts in different build orientations were exposed to steam (under pressure) and air across multiple temperature and time points for the purposes of accelerated aging through oxidative and hydrolytic breakdown. Exposing parts to steam dramatically altered the internal microstructure and functional properties such as the glass transition temperature, tensile properties, and damping behavior. Notably, post-aging XCT revealed large microstructural changes after only 40 h of steam treatment relative to the as-printed specimens. Furthermore, pore reorganization and changes in crystallinity occurred regardless of whether the steam temperature was aggressive enough to induce a significant loss in mechanical properties. The build orientation dependence on the aging rate was minimal with the relative trend in performance persisting across most metrics among the different orientations even after aging.

Theoretical Insights into the Initial Hydrolytic Breakdown of HKUST-1

HKUST-1, i.e., Cu3(BTC)2 (BTC = benzene-1,3,5-tricarboxylate), has been considered as one of the very promising copper-paddlewheel-based metal–organic frameworks (CP-MOFs) for a variety of practica...

Role of Phosphodiesterase 5 (PDE5) in Breast Cancer Stroma: Implications for Targeted Therapy

Breast cancers are heterogeneous tissues comprised of multiple components, including tumor and microenvironment cells. Cancer‐associated fibroblasts (CAFs) are an important cell type in tumor‐associated stroma with multiple roles in tumor initiation and promotion. While the significance of CAFs is well recognized, the treatment of CAFs in clinical practice has not yet been established. Our previous studies have shown that the overexpression of phosphodiesterase (PDE) 5, a metallohydrolase which catalyzes the hydrolytic breakdown of cGMP, enhances the invasive potential of breast cancer cells and reduces survival in breast cancer patients. To extend these observations, we propose to assess the function of PDE5 in tumor microenvironment, to further highlight the potential benefit of targeting PDE5.Our results evidenced, for the first time, PDE5 mRNA and protein expression in CAFs isolated from biopsies of primary human breast tumors. PDE5 expression is increased in human breast cancer stroma compared with normal breast stroma and was correlated to a shorter overall survival in patients. Treatment with PDE5 inhibitors (i.e. sildenafil and tadalafil) significantly inhibited CAF proliferation, motility and invasiveness. To better examine the significance of PDE5 expression in stromal fibroblasts, PDE5 was stably integrated into mouse embryonic fibroblasts (MEFs) and cell proliferation, motility and invasion were investigated. PDE5 transformed MEFs towards a cancer‐associated fibroblast phenotype, as evidenced by increased expression of CAF markers along with enhanced proliferative, migratory and invasive capabilities. Coculture experiments showed that proliferation and motility of human breast cancer cells was increased by PDE5‐overexpressing MEFs compared to vector‐expressing MEFs, suggesting that stromal PDE5 contributes to heterotypic communications within breast cancer. An enriched production of the chemokine CXCL16 was revealed in PDE5‐expressing clones, as evidenced by cytokine array and confirmed by realtime PCR, suggesting a role for this molecule in mediating the tumor‐promoting effects of PDE5 expression in breast stroma. In line with these findings, exposure of CAFs to PDE5 inhibitors was associated with a reduced expression of CXCL16. More importantly, expression of CXCL16 in breast cancer stroma showed a strong correlation with PDE5 as well as with a poor patient survival.In conclusion, PDE5 is overexpressed in breast cancer stroma and enhances the tumor‐stimulatory activities of fibroblasts, highlighting this enzyme as a novel prognostic candidate and an attractive target for future therapy in breast cancers, having already addressed the delivery, stability, and toxicity issues of PDE5 inhibitors in other diseases.Support or Funding InformationMy First AIRC Grant (MFAG) #16899 to I. BaroneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

How bone degradation, age, and collagen extraction methods affect stable isotope analysis

Stable isotope analysis from bone collagen and carbonate is a crucial tool in archaeometry for dietary and provenance studies. However, an expedient evaluation and interpretation of results have to rely on the integrity of the isotopic values, reflecting the in vivo signal of the tissue. In this context, postmortem bone breakdown can affect measurement results and add uncertainty. This study investigates the effects of bone breakdown and the use of two different extraction methods on the isotopic composition of carbon, nitrogen, and oxygen from collagen and the structural carbonate. The main goal of this study was to test the efficiency of commonly applied quality markers to identify alterations of the isotopic in vivo signal in the organic and inorganic bone fraction. Three fresh human femur diaphyses from different age groups with a known in vivo signal were degraded experimentally to simulate diagenetic processes. One batch was heated in water to induce hydrolytic breakdown; the other one was inoculated with several aerobic and anaerobic bacterial strains for biodeterioration. Furthermore, 60 long-bone samples from natural burial conditions, representing different age groups and burial times, were analyzed. The collagen extraction method proved to have a relevant effect. For bones already compromised by degradational processes, the common gelatin extraction protocol using pulverized bone and a 1 M HCl demineralization step was shown to be too harsh and damaging to the extract. Additionally, the age of the individual might play a role in the resistance of the tissue against degradational factors. The investigation of the commonly used quality criteria revealed that the C/N molar ratio is well suited to identify diagenetically modified isotopic data from collagen carbon and nitrogen. However, no valid marker could be assessed for the reliable prediction of altered δ18O values from the structural carbonate fraction, but oxygen isotopic values proved to be considerably affected by in vitro degradation.

The disastrous copper. Comparing extraction and chelation treatments to face the threat of copper-containing inks on cellulose

Iron gall inks are known to be detrimental to the permanence of historic documents. Among the transition metals present, copper is the greatest threat and an open challenge due to the lack of Cu-specific treatments. In this study, we address the inhibition of copper by comparing extraction (a newly proposed glucose-based treatment) vs. chelation (phytate-based) approaches in terms of performances in scavenging copper and slowing the degradation rate, and of possibly induced side effects. Results show that the glucose treatment partially extracts copper, but it causes long-term damages to paper, i.e. increased fragility and discoloration. The phytate protocol was found beneficial in inhibiting the catalytic activity of copper-rich inks. It limits both long-term oxidation and hydrolytic breakdown of samples without compromising the visual appearance.