The paper summarizes the current knowledge about the structure, species, and content differ-ences of β-D-glucans as a storage and functional component, especially of cereal grains. The pa-per also provides comprehensive information on the biosynthesis of this plant cell wall polysac-charide, genetic and non-genetic factors influencing the content variability and indicates the pos-sibilities of breeding modern varieties with a defined content of this metabolite. The final part of the text is also devoted to the influence of significant technological processes applied to cere-als containing β-D-glucans. The chapter discusses the influence of these processes on the content and structure of the polysaccharide and the resulting changes in its physicochemical properties. Part of the discussed issue are the possibilities of effective application of β-D-glucans in different food products.

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in pre-clinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultra-high throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified 5 selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These are the most selective inhibitors of meprin α to date.

Arylsulfatase and β-glucuronidase are two important enzymes in human, which play important role on dynamic equilibrium of steroidal estrogens. This work probably for the first time reported that hydrogen peroxide (H2O2), hypochlorite and peracetic acid (PAA) could effectively inhibit the activities of arylsulfatase and/or β-glucuronidase. The 50 percent of inhibitions (IC50) of H2O2, and PAA on arylsulfatase were found to be 142.90±9.00, 91.83±10.01, and 43.46±2.92 μM, respectively. The corresponding respective IC50 of hypochlorite and PAA on β-glucuronidase were 704.90±41.40 and 23.26±0.82 μM, while H2O2 showed no inhibition on β-glucuronidase. It was further revealed that the inhibition of hypochlorite on both arylsulfatase and β-glucuronidase was irreversible. On the contrary, the inhibition by H2O2 and PAA was reversible. Moreover, it was found that the inhibitions of arylsulfatase and/or β-glucuronidase by these three chemicals were pH-dependent, among which the inhibition by H2O2 was competitive and non-competitive for PAA. In general, H2O2 and hypochlorite can be endogenously produced in human, which suggested that the two compounds are potential endocrine disruption compounds (EDCs) as they can cause endocrine disruption via inhibition of arylsulfatase and β-glucuronidase. This work further indicated that any agent that can induce production of H2O2 or hypochlorite in human is potential EDC, which explains why some EDCs with very weak or no estrogenic potency can cause endocrine disruption that confirmed in epidemiological studies.

SAA is an acute phase protein that elevates under inflammatory circumstance. The serum level of SAA was associated with the progression of inflammation in numerous diseases. However, little attention was paid to the correlation between SAA and ONFH. In this study, SAA was found risen in the femoral head of osteonecrosis patients through proteomics analysis and further confirmed by ELISA. Furthermore, SAA was proven affecting bone metabolism in rBMSCs. It facilitated the proliferation of rBMSCs whereas it suppressed the osteogenic differentiation of rBMSCs and accelerated the adipogenic differentiation of rBMSCs. Thus, we deem that serum amyloid A, which is a vital acute phase protein in inflammation, affected bone metabolis and plays an imperative role in the pathophysiological process of ONFH.

Plants produce specific structures constituting a barrier hindering penetration of pathogens, while they also produce substances inhibiting pathogen growth . These compounds are secondary metabolites, such as phenolics, terpenoids, sesquiterpenoids, resins, tannins and alkaloids. Bioactive compounds are secendary metabolities from trees and shrubs are used in medicine, herbal medicine and cosmetology. To date fruits and flowers of exotic trees and shrubs have been primarily used as sources of bioactive compounds. In turn, search for new sources of bioactive compounds is currently focused on native plant species due to its availability. Application of such raw material needs to be based on knowledge of their chemical composition, particularly health-promoting or therapeutic compounds. Research conducted to date on European trees and shrubs has been scarce. This paper presents results of literature studies conducted to systematise knowledge on bioactive compounds found in trees and shrubs native to central Europe. The aim of this review providing available information on the subject is to indicate gaps in the present knowledge.

Dunaliella salina is a rich source of 9-cis β-carotene, which has been identified as important in the treatment of retinal dystrophies and other diseases. We previously showed that chlorophyll absorption of red light photons in D. salina is coupled to oxygen reduction and phytoene desaturation and increases the pool size of β-carotene [1]. Here we show for the first time that growth under red light also controls conversion of extant all-trans β-carotene to 9-cis β-carotene by β-carotene isomerases. Cells illuminated with red light from a light emitting diode (LED) during cultivation contained a higher 9-cis β-carotene content compared to cells illuminated with white or blue LED light. The 9-cis/all-trans β-carotene ratio in red light treated cultures reached >2.5:1 within 48 hours and was independent of light intensity. Illumination using red light filters that eliminated blue wavelength light also increased the 9-cis/all-trans β-carotene ratio. With norflurazon, a phytoene desaturase inhibitor which blocked downstream biosynthesis of β-carotene, extant all-trans β-carotene was converted to 9-cis β-carotene during growth with red light and the 9-cis/all-trans β-carotene ratio was ~2:1. With blue light under the same conditions, 9-cis β-carotene was likely destroyed at a greater rate than all-trans β-carotene (9-cis/all-trans ratio 0.5:1). Red light perception by the red light photoreceptor, phytochrome, may increase the pool size of anti-oxidant, specifically 9-cis β-carotene, both by upregulating phytoene synthase to increase the rate of biosynthesis of β-carotene and to reduce the rate of formation of reactive oxygen species (ROS), and by upregulating β-carotene isomerases to convert extant all-trans β-carotene to 9-cis β-carotene.

This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNP), varying in size, against E. coli, S. aureus, E. faecalis, C. albicans, and clinical isolates of Mycobacterium tuberculosis (MTB), as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNP were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (Dynamic Light Scattering, DLS) and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; besides a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNP inhibited MTB growth at 300 μg for 116.6 nm particles and 400 μg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 μg. The results indicate that CNP possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity, but given their instability in solution, the use of lyophilized Allium sativum powder is preferable.

Background: Multiple drug delivery systems obtained by loading nanoparticles (NPs) with different drugs with different physicochemical properties present a promising strategy to achieve synergistic effects between drugs or overcome undesired effects. This study aims to develop a new NP by loading Quercetin (Que) and valproic acid (VPA) onto chitosan. In this context, our study investigated the antioxidant activities of chitosan NPs loaded with single and dual drugs containing Que against oxidative stress. Method: The synthesis of single (Que or VPA) and dual-drug (Que and VPA) loaded chitosan NPs, characterization of the NPs, conducting in vitro antioxidant activity studies, and analysis of the cytotoxicity and antioxidant activity of the NPs in SH-SY5Y cell lines were performed. Result: The NP applications that protected cell viability to the greatest extent against H2O2-induced cell damage were, respectively, 96 µg/ml of Que-loaded chitosan NP (77.30%, 48 h), 2 µg/ml of VPA-loaded chitosan NP (70.06%, 24 h), 96 µg/ml of blank chitosan NP (68.31%, 48 h), and 2 µg/ml of Que and VPA-loaded chitosan NP (66.03%, 24 h). Conclusion: Our study establishes a successful paradigm in developing drug-loaded NPs, with uniform and homogeneous distribution of drugs onto NPs. Chitosan NPs loaded with both single and dual drugs possessing antioxidant activity were successfully developed.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

The suspension cross-linking technique has been utilized to create the magnetic chitosan nanoparticles, which were then applied to the magnetic carrier method at 80°C. First the FeCl2 and FeCl3 solution co-precipitated and synthesized Fe3O4 for utilization in the formation of magnetic chitosan nanoparticles, it has been characterized by utilizing DLS (Dynamic light scattering), XRD (X-ray diffraction spectrometer), FTIR (Fourier transform infrared spectroscopy), which identified structure, size, FE-SEM (Field Emission Scanning Electron Microscope) and HR-TEM (High-resolution transmission electron microscopy) which identified structure and particle size whereas magnetic behavior of chitosan nanoparticles was determined by VSM (Vibrating sample magnetometer). According to the results collected, the magnetic chitosan nanoparticles have been spherical in form and size ranging from around 250 to 400 nm.

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore anti-obesity effect of A. bisporus extract (H2Oslim®) abundant in polysaccharides and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with H2Oslim® and chitosan. Treatment with H2Oslim® and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, H2Oslim® at 80 mg/kg body weight (BW)/day, and H2Oslim® at 160 mg/kg BW/day. H2Oslim® does-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high fat diet (HFD), an HFD with H2Oslim® at 80 mg/kg BW/day, H2Oslim® at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases of body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, H2Oslim® or chitosan administration ameliorated these increases. H2Oslim® or chitosan signifi-cantly reduced dietary efficiency and increased fecal excretion levels of lipid, triglyceride, and total cholesterol. These in vitro and in vivo findings suggest that H2Oslim® might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.

The present study produced and characterised chitosan, chitosan nanoparticle, chitosan n – benzaldehyde Schiff base, chitosan nanoparticle n – benzaldehyde Schiff base, Fe(III) chitosan n – benzaldehyde Schiff base and Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base for biomedical application as antimicrobial agents. The materials were characterized with Fourier Transform Infrared spectroscopy, X-ray Diffractogram and biologically evaluated using disc diffusion method with three gram-positive bacteria. The FTIR absorption peaks were shifted to a lower wave number than the micro materials from which it was modified. These clearly indicate the linkage between phosphate, ammonium ion, Schiff base and Fe(III) metal. The diffracted peaks of Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base were new peaks at 2θ = 24o and 42o when compare to the peak of Fe(III) chitosan n – benzaldehyde Schiff base of 2θ = 22.5o and 34o. The difference in peak shift were attributed to the ionic bonding of the complexation of Fe(III) with the blending of benzaldehyde to chitosan – Tpp backbone structure. Fe(III) chitosan nanoparticle Schiff base has more antimicrobial activity against same bacteria and fungi tested than Fe(III) chitosan n – benzaldehyde Schiff base, chitosan n – benzaldehyde Schiff base and chitosan. The antimicrobial activities of the synthesised six materials shown that the materials have high activities than the above – mentioned standard drugs.

The purpose of this study is to identify the steps involved in fabricating silica/chitosan composite membranes and their suitability in fuel cell application. It also intends to identify the physical characteristics of chitosan composite membranes, including their degree of water absorption, proton conductivity, methanol permeability, and functional groups. In this investigation, composite membranes were fabricated using the solution casting method with chitosan content of 5 g and silica variations dosage of 2% and 4% while stirring at a constant speed for 2h. According to the findings, the analysis of composite membranes produced chitosan membranes that were successfully modified with silica. The optimum membrane was found to be 4% s-SiO2 from the Sol-gel method with composite membrane's optimal condition of 0.234 cm/s proton conductivity, water uptake of 56.21%, and reduced methanol permeability of 0.99 × 10 -7 cm2/s in the first 30 minutes and 3.31 × 10-7 in the last 150 minutes. Maintaining lower water uptake capacity at higher silica content is still a challenge that needs to be addressed. However, the fabricated membranes showed exceptional results in terms of proton conductivity and methanol permeability.

This study revealed the synthesis of cross-linked chitosan/Citrus reticulata peel waste (C/CRPW) composites that could be used as low-cost and green bio-adsorbents for the removal of Congo red (CR) dye from aqueous solutions. C/CRPW composites containing different amounts of Citrus reticulata peel waste (CRPW) and chitosan were prepared and cross-linked with glutaraldehyde. The composites were characterized by FESEM, FTIR, and BET. The C/CRPW composites as a new type of bio-adsorbents displayed superior adsorption capability toward anionic CR molecules and the adsorption capacities increased by incorporation of CRPW. Effects of different ambient conditions such as contact time, pH, adsorbent dosage, initial adsorbate concentration, and temperature were fully studied. The conditions which obtained 43.57 mg/g of the highest adsorption capacity were conducted at pH 4, initial concentration of 100 mg/L, adsorbent dosage of 2.0 g/L, and contact time of 24 hours at 328 K. The adsorption data was found to follow the pseudo-second-order kinetic model and the Freundlich isotherm model. According to the findings of this investigation, it was observed that the C/CRWP composites can be used as adsorbents due to their advantages of simple preparation process, environmentally friendly, renewable, efficient, and low-cost.

The influence of pH, temperature, biopolymer ratio, total concentration, and ionic concentration on the interaction between egg white protein (EWP) and chitosan (CS) was investigated through turbidity, zeta potential, and state diagram in our research. In addition, phase behavior was observed under various conditions. The turbidity of EWP remained low (turbidity<0.03) and basically unchanged at a wide range of pH (4.0-8.0), while the turbidity of CS was slightly higher (turbidity<0.2) after pH 7.0 than before. Moreover, under the same conditions, a sharply rising peak pattern was observed for the complex between EWP and CS. The maximum turbidity value was observed at 55°C, and the temperature had a mild effect on turbidity. The optimum EWP to CS ratio was found to be 12:1 based on the experiment of the turbidity curves and state diagrams influenced by different biopolymer mixing ratios. With the enhanced concentrations of total biopolymer, the maximum turbidity rose insignificantly above 0.1%.

Green microalgae including those from the genus Lobosphaera are exploited in biotechnology to obtain valuable fatty acids e.g., arachidonic acid (C20:4, ARA) for the production of infant formulae, food and feed additives. In nature, microalgae frequently exist in naturally immobilized state (as biofilms) with limited cell division rate and increased stress resilience. In biotechnology, immobilization of microalgae on artificial cell carriers simplifies biomass harvesting, increases culture robustness and productivity. The choice of suitable cell carrier is central to biotechnology of immobilized culture. Cell carriers based on the natural amine-containing polymer chitosan and synthetic polyethylenimine (PEI) are promising candidates for immobilization of phototrophic microorganisms. This is the first report on the effects of immobilization on PEI and chitosan on the accumulation and composition of polyunsaturated fatty acids, including ARA, in Lobosphaera sp. IPPAS C-2047. The immobilization on PEI increased ARA percentage in the total tatty acids and ARA accumulation by 72% and 81%, compared with the suspended cells cultured respectively in complete or nitrogen-deprived medium 14 days. Immobilization of Lobosphaera sp. on the chitosan-based carrier declined ARA but increased oleic and α-linoleic acid percentages. Mechanisms of the effects of immobilization on fatty acid profiles of the microalgae are discussed.

Active films based on carboxymethyl chitosan incorporated corn peptide were developed. Physicochemical properties of the films, including thickness, opacity, moisture content, color, mechanical properties, water vapor permeability, and oil resistance, were measured. Biological activities of the films, including the antioxidant and antibacterial activities, were characterized in terms of 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging activity, reducing power, the total antioxidant activity, and the filter disc inhibition zone method. The results indicated that the incorporation of corn peptide caused interactions between carboxymethyl chitosan and corn peptide in Maillard reaction and gave rise to the films light yellow appearance. Compared with the Control, the degree of glycosylation, browning intensity, thickness, opacity, tensile strength, antioxidant activity, and antibacterial activity of films were increased, but the elongation, vapor permeability, and oil resistance of films were decreased. The films based on corn peptide and carboxymethyl chitosan can potentially be applied to food packaging.

Scaffolds are widely used in tissue engineering because their manufacture is based on natural and synthetic polymers, which allows them to have properties such as biocompatibility and biodegradability, creating an ideal environment for cell growth on their surface. In this context, among the polymers studied in Tissue Engineering are Chitosan (CH) and Polyvinyl Alcohol (PVA). CH is a versatile polymer obtained from de-acetylation of chitin, which is used for its high biodegradability and biocompatibility, although its mechanical properties must be improved. It has been found that one of the ways to improve the mechanical properties of CH is to mix it with other synthetic polymers such as PVA. PVA is known for its biocompatibility, biodegradability, zero toxicity and ease of preparation due to its solubility in water and excellent mechanical properties, such as tensile strength and ease in the formation of films and barriers. In this study we evaluated the capacity of scaffolds made with CH and PVA in different concentrations (2: 1, 1: 1, 1: 2, respectively) as a possible application in bone regeneration. This was made through different characterization tests such as Infrared Spectroscopy, AFM, Swelling test and Porosity test, where we obtained information about its structural and physicochemical properties. Additionally, a cellular quality control was performed on the material through the MTT assay. The Fourier transform infrared spectroscopy (FTIR) study showed that there are strong intermolecular hydrogen bonds between the chitosan and polyvinyl alcohol molecules. The Swelling and Porosity tests showed favorable results, obtaining maximum values ​​of 5519% and 72.17% respectively. MTT tests determined that the prepared materials are not cytotoxic. These findings suggest that scaffolds possess properties suitable for use in Tissue Engineering.

The recovery and valorization of waste are some of the key aspects of sustainable production. The crustacean exoskeletons can be potentially used to obtain value-added products such as chitosan. A comprehensive analysis including both safety and sustainability aspects of chitosan production from shrimp shells is presented in this study. The inherent safety analysis and sustainability evaluation was performed using the Inherent Safety Index (ISI) methodology and the Sustainable Weighted Return on Investment Metric (SWROIM), respectively. The process was designed for a processing capacity of 57,000 t/y according to shrimp production in Colombia. The economic (%ROI), environmental (PEI output), energy (exergy efficiency), and safety (ITI) technical parameters were included in the sustainability evaluation. The three first were obtained from the previous analysis performed by the authors. The total inherent safety index was estimated at 25 indicating that the process is inherently unsafe. The main process risks were given by the dangerous substance, reactivity, and inventory subindices. The overall sustainability evaluation showed a SWROIM of 36.23% indicating that the case study showed higher weighted performance compared to the return on investment (ROI) metric of 18.08%.

The purpose of this study was to investigate the effect of chitosan (CS) and Alginate (Alg) polymers concentrations and CaCl2 concentration on metronidazole (MET) drug loading (LE), size particles and zeta potential. Nanocomposites were prepared by ionotropic pregelation method. A (21 *31 *21) *3= 36 full factorial design (FFD) was used to predict statistical equation and responses. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscope and in vitro drug release studies. All data indicated the presence of drug into MET-CS-AlgNPs nanocomposites. The release profile of MET-CS-AlgNPs nanocomposites was found to be sustained

Electrospinning is the versatile technique to generate large quantities of micro- or nano-fibers from a wide variety of shapes and sizes of polymer. Natural bone is a hierarchically composites with the dispersion of inorganic ceramic along organic polymer. The aim of this study, the electrospun poly (lactic acid) (PLA) mats coated with chitosan (CH) and calcium silicate (CS) powder were fabricated. The morphology, chemical composition, and surface properties of CS/CH-PLA composites were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. In vitro, the CS/CH-coated PLA mats increased the formation of apatite on the surface when soaking in cell cultured medium. During culture, the adhesion and proliferation of the human mesenchymal stem cells (hMSCs) cultured on CS/CH-PLA were significantly promoted relative to those on PLA. Collagen I and fibronectin levels and promoted cell adhesion were observed upon an increase in CS content. Further, compared to PLA mats without CS/CH, CS10 and CS15 mats markedly enhanced the proliferation of hMSCs as well as their osteogenesis properties, which was characterized by bone-related gene expression. Our results demonstrated that the biodegradable and electroactive CS/CH-PLA mats had potential application as an ideal candidate for bone tissue engineering. Together, findings from this study clearly demonstrated that PLLA-C2S composite scaffold may function as an ideal candidate for bone tissue engineering.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

The protein TRPM8, a non-selective, calcium (Ca2+) permeable ion channel is implicated in several pathological conditions, including neuropathic pain states. In our previous research endeavors, we have identified β–lactam derivatives with high hydrophobic character that exhibit potent and selective TRPM8 antagonist activity. This work describes the synthesis of novel derivatives featuring C-terminal amides and diversely substituted N’-terminal monobenzyl groups, in an attempt to increase the total polar surface area (TPSA) in this family of compounds. The primary goal was to assess the influence of these substituents on the inhibition of menthol-induced cellular Ca2+ entry, thereby establishing critical structure-activity relationships. While the substitution of the tert-butyl ester by isobutyl amide moieties improved the antagonist activity, none of the N’-monobencyl derivatives, regardless of the substituent on the phenyl ring, achieved the activity of the model dibenzyl compound. The antagonist potency of the most effective compounds was subsequently verified using Patch-Clamp electrophysiology experiments. Furthermore, we evaluated the selectivity of one of these compounds against other members of the TRP ion channel family and some receptors connected to peripheral pain pathways. This compound demonstrated specificity for TRPM8 channels. To better comprehend the potential mode of interaction, we conducted docking experiments to uncover plausible binding sites on the functionally active tetrameric protein, which come upon four main poses by the pore zone, differents from those described for other known antagonists. Finally, in vivo experiments, involving a couple of selected compounds, revealed significant antinociceptive activity within a mice model of cold allodynia induced by oxaliplatin.

Forty-five male Dorper crossbred lambs (40.17 ± 0.35 kg BW) were used in order to investigate the effects of the duration of calcium propionate (CaPr) supplementation in lambs finished with zilpaterol hydrochloride (ZH) on the productive performance, carcass characteristics, and meat quality. Lambs were individually housed and fed a finishing-diet for 42 d before being slaughtered. Lambs received the following treatments: 1) No additives (CTL), 2) ZH supplementation for 28 d (with 3 d ZH withdrawal before slaughter) at a dosage of at 7.2 mg/kg diet (ZH), for treatments 3, 4, and 5, lambs received ZH and 10g CaPr/lamb/d throughout the entire phase (42 d), or during the last 28 or 14 d before slaughter. Compared to CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr and ZH exhibited quadratic increases (p < 0.05) in final BW (FBW), ADG, and dressing percentage (D%). These increases were optimal at an estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p < 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p <0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p < 0.05), being higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PLR) also increased linearly (p < 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight and some whole cuts. However, it can also have a negative effect on PRL%.

This study presents an innovative analytical method for the detection and quantification of 14 β-agonists in pork using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method involves the use of a solid phase microextraction (SPME) probe, consisting of a wooden tip coated with polyacrylonitrile (PAN) and molecularly imprinted polymer (MIP). This probe has been integrated into an automated extraction device, designed in our laboratory to extract the target analytes prior to LC-MS/MS analysis. Compared to the traditional solid-phase extraction (SPE) procedure, the proposed approach significantly reduces the costs related to adsorbent ma-terial and solvent consumption, and shortens purification time, thereby reducing both the tech-nical workload and associated expenses. The methodology has been carefully validated in ac-cordance with the National Standard of the People's Republic of China (GB/T 22286-2008), evalu-ating key parameters including the limit of detection (LOD), limit of quantification (LOQ), matrix effects, linearity, and both intra-day and inter-day precision. The average recovery rates for all β-agonists were observed to lie between 71.6% and 82.2%, with relative standard deviations (RSDs) consistently below 15% for both types of precision. The LOD and LOQ values were found to range from 0.09 to 0.39 μg/kg and 0.27 to 0.99 μg/kg, respectively. In terms of accurate detection of positive samples, the developed method demonstrated a closer approximation to the true value of the sample compared to the National Standard method GB/T 31658.22-2022. Overall, the proposed method exhibits substantial promise for the routine assessment of β-agonists in pork and presents a practical alternative for compliance monitoring in regulatory settings.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM) - Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus - cultivated on a barley medium, was assessed for its anti-AD effects. A neuron-like PC12 cells, which were subjected to Zn2+, an Aβ aggregator, was employed as an in vitro AD model. The cells pretreated with or without MMMM assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and increment in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaques accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation, and neuroinflammation, by impeding Aβ-induced neurotoxicity.

β-thalassemia, a congenital genetic hematological disorder characterized by decreased or absence of β-globin chains, leads to decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications arising due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to the iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, we critically evaluate the therapeutic efficacy of different iron chelators, emphasizing their respective advantages in managing iron overload complications. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia.

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥ 1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, β-HCG, and HbA1C was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with increase in β-HCG and HbA1C, and decrease of total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of N-sulfonyl-1,2,3-trizaoles with β-enaminones. The imidazole ring was formed through 1,1-insertion of N-H bond to α-imino rhodium carbene and subsequential intramolecular 1,4-conjugate addition when α-carbon atom of amino group bearing with methyl, whereas utilizing phenyl substituent constructed pyrrole ring via intramolecular nucleophilic addition. Features such as mild conditions, good functional groups tolerance, gram-scale synthesis, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of N-heterocycles.

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.

The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC₅₀ value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

As a chronic disease, osteoarthritis (OA) leads to degradation of both cartilage and subchondral bone, of which the development is related to proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of Specnvezhenide in osteoarthritis and mechanism of it was studied in vitro and in vivo. The results showed that Specnvezhenide decreases interleukin-1β-induced expression of matix-degrading enzymes and reduces the activation of NF-κB and wnt/β-catenin pathways in vitro. Furthermore, Specnvezhenide treatment prevents the degeneration of both cartilage and subchondral bone in rats OA model. As conclusion, to the best of our knowledge, we report firstly that Specnvezhenide decreases interleukin-1β-induced inflammation on rat chondrocytes by inhibiting activation of NF-κB and wnt/β-catenin pathways, and has therapeutic potential in OA treatment.

Environmental estrogen pollution and estrogen effects on the female reproduction system are well-recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproduction system. 17 β-estradiol is carcinogen and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects the psychological well-being such as depression, fatigue and others. Thus, a simple method of detection of 17 β-estradiol will be important for both environmental estrogen pollution and women’s health care. This study demonstrates a simple-use, cost effective 17 β-estradiol biosensor system which can be used for both environment and women’s health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe (CN) ₆/K₄Fe (CN) ₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER- α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied was between 2.25 pg/mL to 2,250 pg/mL, Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulate urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone which has a similar chemical structure and molecular weight as those of 17 β-estradiol was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

Targeting drugs to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier. (BBB). The cutting edge in nanotechnology generates optimism to overcome the growing challenges in biomedical sciences through effective engineering of nanogels. The primary objective of the present report was to develop and characterize biocompatible natural chitosan (CS)-based NG that can be tracked thanks to the tricarbocyanine (CNN) fluorescent probe addition of the biopolymer backbone. FTIR shed light on the chemical groups involved in the CS and CNN interactions and between CNN-CS with tripolyphosphate, the cross-linking agent. Both in vitro and in vivo experiments were carried out to determine if CS-NG can be utilized as therapeutic delivery vehicles directed towards the brain. An ionic gelation method was chosen to generate cationic CNN-CS-NG. DLS and TEM confirmed that these entities size fell into nanoscale. CNN-CS-NG was found to be non-cytotoxic as determined in the SH-SY5Y neuroblastoma cell line through biocompatibility assays. After cellular internalization, the occurrence of an endo-lysosomal escape (a crucial event for an efficient drug delivery) of CNN-CS-NG was detected. Furthermore, CNN-CS-NG administered intraperitoneally to female CF-1 mice were detected in different brain regions after 2 h of administration using fluorescence microscopy. To conclude, the obtained findings in the present report can be useful in the field of neuro-nanomedicine when designing drug vehicles with the purpose of delivering drugs to the CNS.

Silver ion (Ag+) are recognized for their potent antibacterial properties; however, their utilization in food preservation is restricted by factors such as inadequate stability, a transient antibacterial impact, and the potential for human absorption. Hydrogel-based antibacterial agents are capable of exerting their antibacterial effects by establishing appropriate microenvironments, which facilitate the efficient delivery of antimicrobial molecules to the contaminated regions of food. In previous studies, we observed that chitosan (CS) and silver nitrate (AgNO3) were able to reduce Ag+ to silver nanoparticles (AgNPs) with enhanced antibacterial properties. This not only significantly extended the stability of the antibacterial agent but also demonstrated exceptional inhibitory capabilities against pathogenic bacteria, including common grape contaminants such as P. expansum, A. niger, and B. cinerea. Utilizing ultrasound-induced complexation technology, this study has successfully synthesized a chitosan-silver (CS-AgNPs) hydrogel. The efficacy of this hydrogel against the pathogenic fungus responsible for jujube black spot disease has been thoroughly investigated. The morphology structures of CS-AgNPs hydrogels were characterized by TEM, FTIR and UV-vis. The results indicated that AgNPs ranging from 80 to 110 nm were uniformly dispersed within the gel matrix and remained stable for extended periods at room temperature. In vitro antibacterial assays and fractional inhibitory concentration index (FICI) studies revealed that the pronounced antibacterial efficacy of the CS-AgNPs hydrogel was primarily attributed to the additive antibacterial effect of CS and AgNPs. These insights underscore the significant potential of CS-AgNPs hydrogels in combating fungal diseases of jujube, offering innovative strategies and materials for the management of agricultural pathogens.

Fibroin-chitosan composites, especially those containing nanohydroxyapatite, show potential for bone tissue regeneration. The physicochemical properties of these biocomposites depend on the compatibility between their components. In this study, the intermolecular interactions of fibroin and chitosan were analyzed using a molecular dynamics approach. Two types of systems were investigated: one containing acetic acid and the other containing calcium (Ca²⁺) and hydrogen phosphate (HPO₄²⁻) ions mimicking hydroxyapatite conditions. After obtaining the optimal equilibrium structures, the distributions of several types of interactions including hydrogen bonds, ionic contacts, and hydrophobic contacts along with the structural and energetical features were examined. The calculated binding energy values for the fibroin-chitosan complexes confirm their remarkable stability. The high affinity of fibroin for chitosan can be explained by the formation of a dense network of interactions between considered biopolymers. These interactions were found to be primarily hydrogen bonds and ionic contacts involving ALA, ARG, ASN, ASP, GLN, GLU, GLY, LEU, PRO, SER, THR, TYR, and VAL residues. As it was established, the complexation of fibroin with chitosan maintains the β-sheet conformation of the peptide. β-Sheet fragments in fibroin are involved in the formation of significant amount of hydrogen bonds and ionic contacts with chitosan.

The increasing global concern over plastic waste and its environmental impact has led to a growing interest in the development of sustainable packaging alternatives. This study focuses on the innovative use of expired dairy products as a potential resource for producing edible packaging materials. Expired dairy products, which are typically discarded, contribute to food waste and environmental pollution. By modifying these products to packaging materials, a dual-purpose solution addressing both waste reduction and sustainable packaging is evaluated. Expired milk and yogurt were selected as the primary raw materials due to their protein and carbohydrate content. The extracted casein was combined with various concentrations of chitosan while in some cases glycerol was used. The materials were characterized with attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray analysis (XRD) to examine the interactions between the components of the formed binary blend. Scanning electron microscopy (SEM) was used to evaluate the surface morphology of the blends, while dynamic mechanical analysis (DMA) and tensile experiments were conducted to study the thermomechanical properties of the materials. Barrier properties, including water vapor transmission (WVTR) and oxygen permeability (OTR), were measured to assess the materials' potential to preserve food freshness. The findings reveal that expired dairy-based edible packaging materials exhibit promising mechanical properties, comparable to conventional plastic packaging. The barrier properties and especially the zero oxygen permeability of the membranes, indicate that these materials have the potential to effectively protect food products from external factors that could compromise quality and shelf life. The materials show encouraging signs of eco-friendliness, with a notable reduction in environmental persistence compared to conventional plastic packaging.

Silk fibroin (SF) extracted from Bombyx mori cocoons is a biocompatible and biodegradable polymer shows potential as matrices for tissue engineering and regenerative medicine, or con-trolled drug delivery systems. Regenerated fibroin, obtained by removing sericin from natural silk, is water-soluble. Its aqueous solutions can be processed into a variety of materials, for example, fibrous matrices, using the electrospinning method. In this article, the concentration dependences of the properties of aqueous solutions of regener-ated fibroin, that determine the possibility of obtaining electrospun mats for tissue-engineering applications, are studied. A slowdown in the growth of viscosity after a concentration of fibroin of 30% and a decrease in the transparency of the solution were found; this may be due to the on-set of conformational rearrangements: the transition of fibroin from the random coils, charac-teristic for dilute solutions, to the anisotropic conformation of the helix and the appearance of β-pleated sheets. Fibrous mats from regenerated fibroin were obtained from solutions with a concentration of 10 and 20%. Two methods were used to prevent solubility of fibroin-based matrices: conversion of fibroin to the β-conformation by treatment with an ethanol solution and chemical cross-linking with gen-ipin (Gp). The structures of the fibrous samples were studied by AFM and confocal laser scan-ning microscopy. The composition of the moulding solution for the electrospinning of regener-ated fibroin fibrous matrices and the conditions for their modification have been optimised. It has been shown that the composition of fibroin with chitosan contributes to a decrease in the solubility of electrospun fibrous matrices by increasing the number of amino groups available for modification by Gp, and also leads to a decrease in the diameter of the fibers. Electrospun fiber matrices based on regenerated SF, modified by cross-linking with Gp in water-alcohol solutions, promote cell growth and proliferation and may be promising for tissue engineering.

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding, that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as: antibacterial, antifungal, hemostatic, analgesic activity, in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.

Abstract The present work was designed to investigate antiviral potential of novel mono and oligomeric Chitosan derivatives through in-silico approaches to find potent broad-spectrum anti-viral and promising drug candidates against SARS-CoV-2 and augmentation of their mode of action. Chitosan biopolymer and its derivatives were screened virtually against spike glycoprotein and human ACE2 receptor of nCoV-19. HTCC a polymeric Chitosan has been reported to interact with the corona viral Spike (S) protein and blocks its interaction with ACE2 receptor. Better biocompatibility, structural correlations, variation in degree of decetylation and molecular weight of modified Chitosan derivatives are the key attributes for enhancement of anti-viral activity. The Chitosan derivatives constructively interact with viral S protein. N-Carboxy methyl Chitosan (NCMC) among the Chitosan derivatives displayed efficient binding affinity. NCMC, when compared to mHTCC, a monomeric Chitosan for its interaction with the S protein, RBD site and ACE2 receptor, displayed efficient binding affinity with binding energy of -7.9, -6.3 and -7.4; -6.2, -4.8 and -5.5 Kcal/mol respectively. The interaction of S protein with ACE2 and ligand mHTCC-S protein complex and NCMC-S protein complex with ACE2 was calculated through flexible docking resulted in efficient reduction of binding energy from -901.2kJ/mol to -765.06kJ/mol and-814.72kJ/mol respectively, elucidated that the binding affinity of the viral S protein for its receptor ACE2 decreases in the presence of NCMC/mHTCC. The computational study envisages the antiviral efficiency of NCMC, mHTCC and biocompatible Chitosan derivatives for the first time,as preventive intervention against Covid-19.

Starch is a biopolymer with wide potential for the generation of new biodegradable packages due to its high availability and low price. However, due to its weak functional properties, it is necessary to limit the interaction of some hydroxyl, and to evaluate blends with other polymers to improve their performance. Glycerol plasticized acetylated corn starch films were developed by the casting method, and the impact of incorporating chitosan (TPS:CH) at various proportions (75:25, 50:50, and 25:75 v/v) was studied. The effect of the chitosan ratios on the films' physical, mechanical, water vapor barrier, and thermal properties was evaluated. Chitosan protonated amino groups promote the formation of intermolecular bonds, improving the tensile strength, the thermal stability, the water adsorption capacity, and the gas barrier of starch films. Where the film composed of TPS25-CH75 was the one that presented the best barrier to water vapor. These composite films are a good option for development of biodegradable packaging.

Chitosan arouses large interest due to its properties and possible applications. Every year the number of publications and patents based on this polymer increases. Chitosan exhibits poor solubility in neutral and basic media limiting its use in such conditions. Another serious obstacle is directly related to its natural origin. Chitosan is not a single polymer with a defined structure but a family of molecules with differences in their composition, size, and monomer distribution. These properties have a fundamental effect on the biological and technological performance of the polymer. Moreover, some of the biological properties claimed are discrete. In this review, we discuss how chitosan chemistry can solve the problems related to its poor solubility and can boost the polymer properties. We focus on some of the main biological properties of chitosan and the relationship with the physicochemical properties of the polymer. Then, we visit two polymer applications related to green processes: the use of chitosan in the green synthesis of metallic na-noparticles and its use as support in biocatalyst. Finally, we briefly describe how making use of the technological properties of chitosan it is possible to develop a variety of systems for drug delivery

In this work, we designed and fabricated a multifunctional nanocomposite system which consists of chitosan, raspberry-like silver nanoparticles and graphene oxide. Room temperature atmospheric pressure microplasma (RT-APM) process provides a rapid, facile, and environment-friendly method for introducing silver nanoparticles into the composite system. By loading different drugs onto the polymer matrix and/or graphene oxide, our composite can achieve a pH controlled dual drug release with release profile specific to the drugs used. In addition to its strong antibacterial ability against E. coli and S. aureus, our composite also demonstrates excellent photothermal conversion effect under irradiation of near infrared lasers. These unique functionalities point to it’s the potential of nanocomposite system in multiple applications areas such as multimodal therapeutics in healthcare, water treatment, and anti-microbial, etc.

Guava is a vital fruit worldwide, especially in Pakistan, and due to its nutritional value famous in each age group. Due to a very short shelf life, the marketing and export of this fruit faced severe constraints. Therefore, in the current study, edible coating of chitosan (0, 0.5, 1.0, 1.5, and 2.0%) was evaluated on postharvest shelf life when guava fruits were stored (room temperature and 4 °C temperatures) for 12 days. The chitosan treated coating fruits have shown reduced total sugars and malondialdehyde levels compared to untreated control samples. However, a significant difference (p ≤ 0.05) in total sugar and malondialdehyde levels exists between samples stored in m compared to refrigerated temperature (4 °C). The chitosan-coated samples have shown a greater amount of vitamin C, quercetin, rutin, and total phenolic contents than control samples. However, these nutritional parameters' levels were significantly different (p ≤ 0.05) in samples stored at room than samples stored at refrigerated temperature. However, the levels of crude fiber, potassium, and sodium were found statistically nonsignificant (p ≥0.05) in control versus chitosan treated coating treatments. The findings have documented that the coatings of 1.5 and 2.0% were most effective for extension in shelf life and maintaining the nutritional attributes of guava fruit.

The study compared the influence of chitosan sources on rumen fermentation, methane emission and milk production in lactating dairy cows fed a glycerin-based diet. Six, lactating Holstein-Frisian crossbreeds (410 ± 5.0 kg BW, 120 ± 21 day-in-milk), were arranged in a 3 x 3 replicated Latin square design. In addition to control, a 2% chitosan extract supplement and a 2% commercial chitosan supplement of dry matter intake were the treatments. The results denoted that no significant differences on daily dry matter, nutrients or estimated energy intake were noted when cows received different sources of chitosan. Nutrient digestibility was not influenced differently by extraction based or commercial chitosan supplements. The pH, temperature, ammonia nitrogen, blood urea and microbial count were similar among treatments. The different sources of chitosan supplements did not change the totals of volatile fatty acids, acetate and butyrate; in contrast, different chitosan sources influenced (P<0.05) propionate content. The ruminal acetate to propionate ratio was markedly (P<0.05) reduced with chitosan supplement, but no change appeared between sources of chitosan. At 4 hours after feeding, the methane estimation significantly decreased with the addition of chitosan supplementation (P<0.05) compared to the control group. The purine derivatives and microbial protein synthesis were not altered by the treatments. No significant differences existed on milk yield, milk composition or milk urea nitrogen when cows received different sources of chitosan (P>0.05). In sum, supplementing extracted chitosan showed more potential than did commercial chitosan for enhancing economic efficiency and recycling shrimp residues, therefore, reducing environmental waste.

Huge amounts of wastes are generated during shrimp processing, representing approximately 65% of the initial shrimp weight, which can become an environmental problem when accumulated. Residues such as shrimp shells can be processed to obtain value-added products such as chitin, chitosan, astaxanthin, and a nitrogenous extract under the biorefinery concept. In this work, the economic evaluation and the techno-economic sensibility analysis for a mass integrated biorefinery based on shrimp were developed to determine the economic feasibility of the project and to identify the critical techno-economic variables that affect the profitability of the process. The results showed that a biorefinery for the annual processing of 4,113.09 tons of fresh shrimp in Colombia is profitable, with a return on investment percentage (%ROI) equal to 65.88% and a net present value (NPV) of 10.40 MM USD. The process supports decreases of up to 28% in capacity of production and increases of 12% and 11% in the cost of raw materials and variable operating costs without incurring losses, respectively. However, the decrease over 500 USD/t in the shrimp meat selling price is not supported, thus it is mainly recommended to increase the selling price of this product.

The antiradical and antimicrobial activity of lignin and lignin-based films are both of great interest for applications such as food packaging additives. The polyphenol structure of lignin in addition to the presence of O-containing functional groups is potentially responsible for these activities. This study used DPPH assays to discuss the antiradical activity of HPMC/lignin and HPMC/lignin/chitosan films. The scavenging activity (SA) of both binary (HPMC/lignin) and ternary (HPMC/lignin/chitosan) systems was affected by the percentage of the added lignin: the 5% addition showed the highest activity and the 30% addition had the lowest. Both, scavenging activity and antimicrobial activity are depending on the biomass source showing the following trend: organosolv of softwood > Kraft of softwood > organosolv of grass. Testing the antimicrobial activities of lignins and lignin-containing films showed high antimicrobial activities against gram-positive and gram-negative bacteria at 35 °C and at low temperatures (0-7 °C). Purification of kraft lignin has a negative effect on the antimicrobial activity while storage has positive effect. The lignin release in the produced films affected the activity positively and the chitosan addition enhances the activity even more for both gram-positive and gram-negative bacteria. Testing the films against spoilage bacteria that grow at low temperatures revealed the activity of the 30% addition on HPMC/L1 film against both B. thermosphacta and P. fluorescens while L5 was active only against B. thermosphacta. In HPMC/lignin/chitosan films the 5% addition exhibited activity against both B. thermosphacta and P. fluorescens.

One-dimensional nanostructures such as silver nanowires (AgNWs) have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties; however, their application in the prevention of infections linked to bone tissue regeneration interventions has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension and of completely preventing biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as it presents enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into potential clinical applications of these materials.

A nanostructured electrochemical bi-sensor system for analysis of milks has been developed using the Layer by Layer technique. The non-enzymatic sensor [CHI+IL/CuPcS]2, is a layered material containing a negative film of the anionic sulfonated copper phthalocyanine (CuPcS) acting as electrocatalytic material, and a cationic layer containing a mixture of an ionic liquid (IL) (1-butyl-3-methylimidazolium tetrafluoroborate) that enhances the conductivity and chitosan (CHI) that facilitates the enzyme immobilization. The biosensor ([CHI+IL/CuPcS]2-GAO) results from the immobilization of galactose oxidase on the top of the LbL layers. FTIR, UV-vis and AFM have confirmed the proposed structure and cyclic voltammetry has demonstrated the amplification caused by the combination of materials in the film. Sensors have been combined to form an electronic tongue for milk analysis. Principal Component Analysis has revealed the ability of the sensor system to discriminate between milk samples with different lactose content. Using PLS-1 calibration models, correlations have been found between the voltammetric signals and chemical parameters measured by classical methods. PLS-1 models provide excellent correlations with lactose content. Additional information about other components such as fats, proteins and acidity can also be obtained. The method developed is simple and the short response time permits its use in assaying milk samples on-line.

Emergence of more virulent forms of human pathogenic bacteria with multi drug resistance is a serious global issue and requires alternative control strategies. The current study was focused to investigate the antibacterial and antibiofilm potential of ferulic acid grafted chitosan (CFA) against Listeria monocytogenes (LM), Pseudomonas aeruginosa (PA), and Staphylococcus aureus (SA). The present result showed that CFA at 64 µg/mL concentration exhibit bactericidal action against LM and SA (>4 log reduction) and bacteriostatic action against PA (<2 log CFU) within 24 h of incubation. Further studies based on propidium iodide uptake assay, measurement of material released from the cell, and electron microscopic analysis revealed that the bactericidal action of CFA was due to the altered membrane integrity and permeability. CFA dose-dependently inhibited biofilm formation (52-89% range), its metabolic activity (30.8-75.1% range) and eradicated mature biofilms, and reduced viability (71-82% range) of the test bacteria. Also, the swarming motility of LM was differentially affected at sub-MIC concentration of CFA. In the present study, the ability of CFA to kill and alter the virulence production in human pathogenic bacteria will insight a new scope for the application of these biomaterials in healthcare to effectively treat bacterial infections.

Immobilized metal ion affinity adsorbents have been widely used in separation technique to purify proteins. Due to the leakage of metal ion from the adsorbents, there is no metal ion affinity adsorbent for hemoperfusion has been applied to clinical trial. In this study, in order to prevent the leakage of Zn²⁺ loaded from cellulose beads based adsorbent, improve its stability and adsorption capacity for testosterone, Freeze-drying method was used to enhance the porosity of cellulose beads, improve the surface area of the cellulose beads and adsorption capacity for testosterone. Chitosan was used to coat the adsorbents for preventing the leakage of Zn²⁺ loaded and improve the adsorbent’s stability. Moreover, the factors affecting adsorption ability and some components in plasma were also investigated. The results indicate the adsorption ability of the adsorbent can be significantly improved by freeze-drying. After the adsorbent was coated with 0.02% chitosan solution, the highest adsorption percentage reached 48%. During adsorption, the Zn²⁺ concentration in plasma did not rise. In addition, the adsorption percentage for total proteins was below 15%. The results may be caused by the pore size and surface area of the adsorbent enlarged via freeze-drying, and the chitosan solution went into the pores and coated the outer and inner surface of the adsorbent. The adsorbent has a potential clinical application to remove testosterone in patients with recurrent and metastatic prostate cancer.

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, which is one of the most common skin diseases. Acne vulgaris often associates with acne-related bacteria such as <i>Propionibacterium acnes</i>, <i>Staphylococcus epidermidis</i>, <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, some of which exhibit a resistant against commercial antibiotics used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we evaluated <i>in vitro</i> antibacterial activity of chitosan-phytochemical conjugates against acne-related bacteria. Three of chitosan-phytochemical conjugates used in this study showed stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) exhibited the highest antibacterial activity against acne-related bacteria with minimum inhibitory concentration values of 8 μg/mL to 256 μg/mL. In addition, the MICs of antibiotics against antibiotic resistant <i>P. acnes</i> and <i>P. aeruginosa</i> strains were dramatically reduced in the combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration indices clearly revealed a synergistic antibacterial effect between CCA and the antibiotics. Thus, the median ∑FIC values against the antibiotic resistant bacterial strains were ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics.

The present review is a comprehensive update of the synthesis of monocyclic β-lactams via cycloaddition reactions. According to the IUPAC definition of cycloaddition, both elementary and stepwise processes (formal cycloadditions) have been considered. The years 2019-2022 are covered by the cited literature. The focus of the review is on synthetic aspects with emphasis on the structural scope, reaction conditions, mechanistic aspects, and selectivity results. Selected significant data related to biological activities and synthetic applications are also highlighted.

With around one billion of the world's population affected, the era of Metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which, to date there is almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it affects also extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn®) was approved for Metabolic dysfunction associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Despite that a pharmaceutical industry is still lagging behind to develop an ap-proved pharmacologic therapy for MAFLD, research has been recently intensified and many molecules which are underway in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was ap-proved via accelerated procedure for treatment of MAFLD, i.e. of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval.

Cassava Solid waste (Onggok) is a solid waste from the cassava-based tapioca industry, the starch content in Onggok is still 50-80 wt.% of residual starch, which can be used to produce maltodextrin for foods application. Furthermore, using cassava solid waste is beneficial in terms of the cost of raw materials. The starch content in cassava can be modified through enzymatic hydrolysis using α-amylase and β-amylase enzymes at 80oC and pH 5.5. Enzymatic hydrolysis was done using mixed enzymes that varied the concentration of α-amylase at 0,.1% and the β-amylase enzymes at 0.05, 0.1, and 0.5%. the concentration of cassava waste (Onggok) varied from 4%, 7%, 10%, and 13%. The optimum concentration of α-amylase and β-amylase enzymes are 0.1% and 0.1% respectively at time intervals of 1 minute resulting in a dextrose equivalent (DE) value 0f 5.7. The characteristics of maltodextrin were studied using scanning electron microscopy (SEM) to determine the morphology of the starch structure which had changed due to the enzyme hydrolysis. Simultaneous thermal analysis (STA) was studied to determine the Thermal stability of hydrolysis products. Maltodextrin produced from cassava waste (Onggok) has a DE value < 10, which has the potential to be used in the pharmaceutical industry

This review examines the challenges faced by the pig industry, with a specific emphasis on improving the health and growth of weaned pigs. It emphasises the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimise piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it's important to highlight the critical roles played by vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with vitamin D and selenium, providing a valuable dietary option. In conclusion, effective nutritional strategies, including glucans, vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Chrysin, a flavonoid compound, has attracted interest as a therapeutic agent due to its anti-inflammatory, antidiabetic, antidepressant, and particularly its anticancer properties. Although studies have presented findings regarding the anticancer properties of chrysin, research on its molecular mechanisms of action remains largely insufficient. This research aimed to deeply investigate chrysin's effects on the breast cancer cell line, MDA-MB-231, in terms of proliferation, invasion, colony formation, and apoptosis. The XTT test results confirmed chrysin's cytotoxic effect on MDA-MB-231 cells, indicating a 48-hour IC50 value of 115.77 µM. Chrysin induced apoptosis in cells, as evidenced by Annexin V assay, and also reduced their colony-forming and invasion. Gene expression analyses showed elevated levels of APC, AXIN1, AXIN2, GSK3A, GSK3B, CK1α, CTNNB1, as well as apoptosis-related genes CASP3, -7, -9, and BAX. This increase was corroborated by the observed rise in protein levels of caspase 3/7 and GSK3B. Moreover, molecular docking results showed that chrysin interacted with genes in the WNT/β-catenin pathway and exhibited drug-like ADME properties. In conclusion, chrysin exhibits potential anticancer effects against MDA-MB-231 cells. It is hoped that these findings will advance preclinical and clinical studies on chrysin's potential in breast cancer treatment.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Mushrooms have been an invaluable ingredient in terms of food and medicine to humanity since time immemorial. Mushrooms have been shown to be possessing properties such as anti-tumor, antiproliferative, antioxidant, immunomodulatory, anti-diabetic. Traditional Czech republic medicine involved using Piptoporus betulinus in curing colorectal cancer; similarly, fruiting bodies of Inonotus obliquus were employed in Folk medicine in eastern Europe since the 16^th century. The oriental practice of utilizing mushrooms has witnessed an overwhelming attentiveness from the global research fraternity in exploring its wonder substances. Cancer is one of the key problems faced by researchers in finding an efficient medicine without inducing severe health complications. Mushrooms contain a plethora of bioactive compounds involved in tumor inhibition, such as hispolon, lentinan, gannoderic acid, illudin-s, and many more. The current article briefly describes various edible mushrooms with anti-tumorigenic compounds and their effect on the cancer cells of various means.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease. We aimed to determine the effects of lactoferrin intervention on cognitive function from APP/PS1 mice, and possible mechanisms involved in. Both young and middle-aged male APP/PS1 mice were divided into control and lactoferrin group with 16 weeks’ intervention. Lactoferrin intervention had no effects on cognitive function from both young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered post lactoferrin intervention. In regards to gut microbiota profiles, in the young mice, lactoferrin elevated α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter, in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant post Lf intervention via LEfSe analysis. In the middle-aged mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus and Ruminococcus was significantly reduced post Lf intervention, additionally, S24_7, Bacteroidia, Bacteroidetes and Methylobacterium were specific via LEfSe analysis post lactoferrin intervention. In conclusion, dietary lactoferrin might be beneficial for gut microbiota homeostasis although might have no effects on cognition.

Macro and micronutrients, essential for the maintenance of human metabolism, are daily assimilated through the diet. Wheat and other major cereals are a good source of nutrients, such as carbohydrates and proteins, but cannot supply enough amounts of essential micronutrients which includes provitamin A. As vitamin A deficiency (VAD) lead to several serious diseases spread worldwide, the biofortification of a major staple crop, such as wheat, represents an effective way to preserve human health in developing countries. In the present work, a key enzyme involved in the branch of carotenoids pathway producing β-carotene, lycopene epsilon cyclase, has been targeted by a TILLING approach in a “Block strategy” perspective. The null mutant genotype showed a strong reduction in the expression of lcyE gene and also interesting pleiotropic effects on an enzyme (β-ring hydroxylase) acting downstream in the pathway. Biochemical profiling of carotenoids in the wheat mutant lines showed an increase of roughly 75% in β-carotene in the grains of the complete mutant line vs. the control. In conclusions, here we describe the production and the characterization of a new wheat line biofortified in provitamin A obtained through a non-transgenic approach also shading new light on the molecular mechanism governing carotenoids biosynthesis in durum wheat.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

General phytochemical screening of the aerial parts of Consolida orientalis revealed the presence of steroids, terpenes, phenolic compounds, saponins, fatty acids, alkaloids. This study was conducted to investigate the bioactivities of extracts, isolation and identification the compounds from aerial parts of C.orientalis. The main goal of the present study is identifying and characterizing the antioxidant activity of the Consolida orientalis and biological isolation of active terpenoid. Aerial parts of the plant were dried at room temperature and reduced to small pieces, followed by using extraction with ethyl acetate percolation. Tree complementary analysis system was used, DPPH free radical scavenging test, total phenolic metabolites and FRAP. The total phenolic content was 38.83±2.09 mg gallic acid corresponding to g-1 extract with regarding to standard curve (y=0.0054x+0.0488, r2=0.995). IC50 value for DPPH radical – scavenging was 987.11±28.66 mgml-1. The extract was exhibited a medium reducing power compared with Vit C. The isolation and purification was afforded white crystalline powder which was subjected to physical, chemical and spectral identification by IR, ¹H- and ¹³C- NMR and GC-MS. Isolated compound was identified as β-sitosterol. That is a terpenoid with melting point 133.4-134.5 ͦ c and with molecular formula C₂₉H₅₀O.

Chitosan is a biodegradable polymer derived from chitin, that is a versatile material for various biological applications for its attractive properties such as biocompatibility, biodegradability, and non-toxicity. Furthermore, chitosan possesses Second Harmonic Generation properties, that are useful for bio-sensing applications. In this work we explored the possibility to exploit chitosan-based nanospheres as SHG-based bio-sensors, and also as carriers of 89Sr radionuclide, an Active Pharmaceutical Ingredient for radiopharmaceutical treatments in cancer therapy. To load opportunely the Sr ion on the nanospheres, we used a fructose-based Metal Organic Framework, of formula [Sr(C6H12O6)2(H2O)2]Cl2·H2O, because the sugar was able to drive the Sr ions on the chitosan matrix. The Sr-loaded chitosan nanospheres were synthetized, characterized, and their SHG response was measured. The results encouraged us to propose the nanospheres for theranostic purposes, i.e. at the same time valuable for both therapy and diagnostic applications.

The study focuses on the impact of new methods for inhibiting malolactic fermentation in white wines on their analytical and sensory properties. Enological preparations with different mecha-nisms of effect were tested: fumaric acid, chitosan, Estaan (a preparation based on tannin inhibi-tion), medium-chain fatty acids (MCFA), sulphur dioxide and a control variant where malolactic fermentation (MLF) was performed. The samples underwent analysis through HPLC (high-performance liquid chromatography) to determine concentrations of malic and lactic acid, as well as biogenic amines. GC (gas chromatography) analysis was used to monitor volatile sub-stances, alongside sensory evaluation. The study demonstrated a significant influence of indi-vidual enological preparations on the aromatic profile of the examined wines. The SO2 and MCFA variants exhibited the highest concentrations of volatile substances within the esters group, spe-cifically isoamyl acetate, 1-hexyl acetate and phenylethyl acetate. Conversely, the fumaric acid and Estaan variants displayed the lowest concentrations of these esters. The most notable disparities were observed in acetoin concentration, with the MCFA variant exhibiting the lowest values. Additionally, the chitosan variant showed higher concentrations of putrescine and spermidine compared to the MCFA and fumaric acid variants, which presented the lowest levels.

Soil salinity is seen as a major restriction for crop production, and with water scarcity this problem becomes more complicated. Mulching is crucial to salinity dynamics management by decreasing evaporation with improving the soil’s characteristics. Using chitosan as an eco-friendly biostimulant can enhance plant defense genes during different abiotic stresses. Recently, agricultural research has recognized nanoparticles as a pioneer material due to their distinctive physicochemical features. Therefore, a lysimeter experiment was conducted to investigate the interactive effects of mulching (UNM: un-mulched, WPM: white plastic, RSM: rice straw and SDM: sawdust) and chitosan foliar application (Ch0: control, Ch1: 250 mg chitosan L-1, Ch2: 125 mg nano chitosan L-1, and Ch3: 62.5 mg nano chitosan L-1) on the biochemical soil characteristics and common beans productivity under salt affected soil conditions. Organic mulching (RSM and SDM) treatments significantly improved the soil's organic carbon, available nutrient content, and total count of bacteria. WPM treatment lowered soil EC to 6.63 dS m-1 and increased soil water content to 34.13%. The application of Ch3 caused considerable increases in the plant height, shoot dry weight, root dry weight, grain yield, and nutrient content in the seed. The total fungi count in the soil and Na% in the seed was significantly decreased due to chitosan foliar applications. Moreover, the interactive effect of different mulch materials plus foliar by chitosan applications gave a statistically similar seed yield in both seasons. Overall, this study revealed the potential of the mulching treatments and foliar application of nano chitosan in improved biochemical soil characteristics and common bean productivity under saline soil conditions.

Chitin/chitosan and collagen are two of the most important bioactive compounds with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from fish and shellfish non-edible parts, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value-chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications. Overall, research on chitin/chitosan remains focused on the compound itself rather than its market applications. Still, chitin/chitosan use is expected to increase in food and biomedical applications, while that of collagen is expected to increase in biomedical, cosmetic, pharmaceutical, and nutritional applications. Sustainable practices, such as the reuse of waste materials, contribute to strengthen both value-chains; the identified weaknesses include the lack of studies considering market trends, social sustainability, and profitability, as well as insufficient examination of intellectual property rights. Government regulations, market demand, consumer preferences, technological advancements, environmental challenges, and legal frameworks play significant roles in shaping both value-chains. Addressing these factors is crucial for seizing opportunities, fostering sustainability, complying with regulations, and maintaining competitiveness in these constantly evolving value-chains.

The purpose of this research work was to synthesis bio-derived nanocomposite films by incorporating Na0.5Bi0.5TiO3 (NBT) nanoparticles into Chitosan matrix. The NBT nanoparticles were synthesized using a traditional solid-state technique. Then, through a solution casting approach, flexible composite films were fabricated using Chitosan polymer. The morphology and structural assessments were carried out utilizing scanning electron microscopy (SEM), X-ray diffraction and fourier transform infrared technique. The SEM micrographs showed that NBT nanoparticles were randomly distributed and interconnected with other particles, forming interconnected grains with substantial interspaces within the matrix. The spectral response between 300 and 800 nm of the composites is mainly governed by light scattering of NBT particles with diameter sizes in the 100 - 400 nm range and the bandgap of the NBT phase. The dielectric studies demonstrated that the composite films exhibited higher dielectric values compared to the pure Chitosan film. Besides, the increase of NBT amount was found to increase the dielectric values. Additionally, local piezoelectric measurements reveal the expected piezoelectric and ferroelectric behavior for the NBT particles dispersed into the polymer matrix, as locally probed by Piezoresponse Force Microscopy. The studied system bears interest for advanced biocompatible opto- and piezo-electric materials.

The cross-linked microspheres were prepared and loaded with Favipiravir SARS-CoV-2 antiviral drug, by copolymerization of chitosan (CS) with a polysaccharide extracted from fresh pomegranate peels. Moreover, glutaraldehyde (Glu) has been used as chemical cross-linker ,and sodium hexametaphosphate (SHMP) as physical cross-linker. The extracted polysaccharide was analyzed and different techniques have been used and the analyses leads to the fact that it is pectin .The surface morphology of the prepared microspheres was studied use scanning electron microscope where the size and the shape factor (S) of Glu microspheres have shown high values(74.27μm) and (0.852) respectively means their surfaces are tends to roughness, whereas the SHMP microspheres have shown size particle(20.47μm)and shape factor (0.748) which gives indication that the SHMP microspheres have smooth surfaces. The swelling studies have shown that Glu microspheres have higher degree of swelling which means SHMP microspheres are more compact. The prepared microspheres have shown more Loading percentage of Favipiravir antiviral drug in SHMP microspheres(37%w/w)in comparison with Glu microspheres(35%w/w) where the electrostatic interaction between the Favipiravir ions and SHMP anions help for more loading. The microspheres prepared under different types of cross-linking have shown initially burst release of Favipiravir and followed by a step of controlled release for a certain time where its period depends on the pH of the release media. Both Glu and SHMP cross-linked microspheres have shown high controlled release time in buffered release solution of pH 7.4 and for a less periods in pH 1.3 and pH 9.4 which may related to the type of electrostatic interactions between drug and polymer system and their reactions with release solution ions.

Polymeric wet-strength agents are important additives used in the paper industry to improve the mechanical properties of paper products, especially when they come in contact with water. These agents play a crucial role in enhancing the durability, strength, and dimensional stability of paper products. The aim of this review is to provide an overview of the different types of wet-strength agents available and their mechanisms of action. We will also discuss the challenges associated with the use of wet-strength agents and the recent advances in the development of more sustainable and environmentally friendly agents. As the demand for more sustainable and durable paper products continues to grow, the use of wet strength agents is expected to increase in the coming years.

The prospective applications of chitosan-based hydrogels (CBHs), a category of biocompatible and biodegradable materials, in biomedical disciplines such as tissue engineering, wound healing, drug delivery, and biosensing have garnered great interest. The synthesis and characterization processes used to create CBHs play a significant role in determining their characteristics and effectiveness. The processing procedure could be tailored to obtain specific features like porosity, swelling, mechanical strength, degradation rate, and bioactivity, affecting the properties of CBHs to a great extent. Additionally, characterization methods aid in gaining access to the microstructures and properties of CBHs. Especially, this review provides a comprehensive assessment of the state-of-the-art with a focus on the affiliation between particular properties and application domains. The main obstacles and prospects for the future of CBH development for biomedical applications are also covered in the review.

The isolation and potential applications of chitosan from the fungal source is an alternative to crustacean chitosan and synthetic polymers. The strains of Basidiomycota (Heterobasidion annosum, Phanerochaete chrysosporium, Pleurotus ostreatus, Trametes versicolor, Lentinus lepideus) with different environmental distribution, ecological importance, and industrial application were studied for mycelial biomass production in submerged (SF) and solid state fermentation (SSF). Further, the chitosan from fungal cells was extracted and characterized by elemental analyses (nitrogen) and FTIR spectroscopy. The fruiting bodies of Pleurotus ostreatus, Agaricus bisporus and Ganoderma ap-planatum were chosen as a reference material of chitosan content in basidiocarps. Stationary SF gave the lowest biomass yield in comparison with shaken SF and SSF. The role of aeration and agitation in biomass production was clearly observed in shaken SF with the highest yield achieved by P. chrysosporium. The highest biomass yield in SSF produced P. ostreatus and T. versi-color. The content of chitosan within fungal species varied depending on the method of cultiva-tion. The highest chitosan yield among the cultivated strains was obtained from mycelium of P. chrysosporium and T. versicolor in SF. The highest chitosan yield in fungal fruiting bodies demon-strated commercially cultivated mushroom A. bisporus. The extracted chitosan is proposed as functional biopolymer additive for ecological materials to substitute the synthetic wet and dry strength agents in packaging materials.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improve patient adherence. This work aims to develop a suitable chitosan-based scaffold to provide 24 hours controlled release of DKT, by taking advantage of chitosan’s thermo-responsive behavior as well as local hyperthermia in wounds. Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and IR spectroscopy. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C to evaluate the release profiles, which were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 hours (77.75 ± 2.72 %), and reduced the burst release in the initial 6 hours (40.18 ± 1.00 %), while at 38 °C the release reached 88.52 ± 2.07 % at 12 hours. The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed chitosan/gelatin thermo-responsive scaffold provides a suitable system for wound healing with a controlled release of DKT for 24 hour-use, which can overcome adherence issues and wound complications.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

In this work, an enzymatic sensor, based on a bionanocomposite film consisting of a polyelectrolyte complex (PEC) [Chitosan/kappa-carrageenan] doped with gold nanoparticles (AuNPs) encapsulating glucose oxidase (GOD) deposited on a gold electrode (Au) for glucose sensing, is described. Using the electrocatalytic synergy of AuNPs and GOD as a model of enzyme, the variation of the current (µA) as a function of the log of the glucose concentration (log [glucose]), shows 3 times higher sensitivity for the modified electrode (283.9) compared to that of the PEC/GOD modified electrode (93.7), with a detection limit of about 5 µM and a linearity range between 10µM and 7mM. The response of the PEC/AuNPs/GOD based biosensor also presents good reproducibility, stability and negligible interfering effects from ascorbic acid, uric acid, urea and creatinine. The applicability of the PEC/AuNPs/GOD based biosensor was tested in glucose-spiked saliva samples and acceptable recovery rates were obtained.

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

In this work, we synthesized chitosan grafted-poly acrylic acid (CS-g-PA) through surface-initiated atom transfer radical polymerization (SI-ATRP). We also studied the adsorption process of copper and lead ions onto CS-g-PA surface. Adsorption equilibrium studies indicated pH 4.0 as the best pH for the adsorption process, while the maximum adsorption capacity for Pb2+ ions was 98 mg*g-1 and for Cu2+ was 164 mg*g-1, higher adsorption capacities than chitosan alone (CS), where Pb2+ was only 14.8 mg*g-1and Cu2+ was 140 mg*g-1, respectively. Furthermore, the adsorption studies indicated that Langmuir model describes all the experimental data. All these results suggest that the new CS-g-PA polymers had potential as adsorbent for hazardous and toxic metal ions produced by different industries.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infec-tion, underscoring the importance of cellular cholesterol levels not only in the viral entry pro-cess but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellu-lar accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

In the present study, we aimed to observed hair follicle development and describe Wnt10b/β-catenin signaling pathways related to hair follicle development in different ages of Rex rabbits. Six Rex rabbits (3 male and 3 female) of 15, 30, 60, 90, 120 and 150 days of age were selected and skin samples were collected for hair follicle development and Wnt/β-catenin signaling pathway genes expresion detection. The results showed that the the values for body weight, coat length, skin thickness, skin area, and skin weight of Rex rabbits were increased significantly with age (p &lt; 0.05). The total hair follicle density, secondary hair follicle density and the ratio of the secondary hair follicle density to the primary hair follicle density in 120 days of Rex rabbits was higher than that in the other ages (p &lt; 0.05), and the major hair follicles were in the growing period at 15 days and 30 days of age, some of them had already entered the degeneration period at 60 days of age, and most of them entered the degeneration period at 90 days of age, the presence of quiescent hair follicles and the enlargement of primary hair follicles were also observed. At 120 and 150 days of age, the back hair follicles entered the growing period, and the secondary hair follicles had obvious differentiation. Furthermore, the expression of the Wnt10b, CTNNB1, adenomatosis polyposis protein (APC), Disheveled 2 (DVL2), glycogen synthase kinase 3β（GSK-3β）, Lymphoid enhancer-binding factor 1 (LEF1), dickkopf-1 (DKK1) and transforming growth factor beta 1 (TGFβ-1) genes in the skin tissue of Rex rabbits at different age was significantly differences (p &lt; 0.05), and the expression of the Wnt10b, CTNNB1, DVL2, GSK-3β, and TGFβ-1 genes at 90 days was higher than that in the other days, the expression of the LEF1 and DKK1 genes at 60 days was higher than that in the other days. As western blotting indicated, the β-catenin protein phosphorylation (P-CTNNB1) levels in the skin tissue of Rex rabbits shows the trend of first increasing, then decreasing and then increasing, 60 days, 120 days and 150 days significantly higher than 15 days, 30 days or 90 days (p &lt; 0.05). With the increasing of ages, the GSK-3β protein phosphorylation (P-GSK-3β) levels in the skin tissue of Rex rabbits were increasing, and maximum at 120 days of age (p &lt; 0.05). These results show that ages could influence on the fur quality and hair follicle traits of Rex rabbits, and Wnt10b/β-catenin signaling pathways is involved in the biological process of periodic hair follicle development in Rex rabbits. Considering the rule of fur growth, the slaughter age of Rex rabbits should not be earlier than 120 days.

The Wnt/β-catenin signaling deregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of the study was to immunohisto-chemically evaluate and compare the expression of Fzd8, WNT1, GSK-3ß and β-catenin genes in the hearts of rats with spontaneous hypertension (SHR) and DOCA-salt- induced hypertension. The myocardial expression Fzd8, WNT1, GSK-3ß and β-catenin was detected by immunohisto-chemistry and the gene expression was assessed with real-time PCR method. In SHR immunore-activity of Fzd8, WNT1, GSK-3β and β-catenin was attenuated in comparison to normotensive animals. In DOCA-salt immunoreactivity of Fzd8, WNT1, GSK-3β and β-catenin was enhanced. In SHR, decrease in the expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was observed compared to the control group. Increased expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was demonstrated in the hearts of rats DOCA-salt. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. Obtained results may constitute the basis for further research aimed at better under-standing the role of the Wnt/β-catenin pathway in the functioning of the heart.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of &gt;90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of &lt;80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

The purpose of this study was to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women. The subjects for the study were aged 65–70 years, composed of the circuit training group(n=12) and control group(n=11). The 60-minute combined exercise was performed 3 times per week for 16 weeks. Exercise intensity was progressively increased from 40% HRR to 70% HRR. The test data were analyzed by paired t-test, independent t-test, and two-way repeated measures ANOVA, and the alpha level of .05 was set for all tests of significance. The findings of this study were as follows: β-amyloid significantly decreased after the exercise group had compared to before the exercise and BDNF and cognitive function significantly increased after the exercise group had compared to before the exercise. However, there were no significant changes in β-amyloid, BDNF, and cognitive function in the control group Therefore, it is suggested that the circuit training used in this study could be an effective exercise method for improving the risk factors of cognitive impairment in obese elderly Korean women.

The significant environmental issue of water pollution caused by emerging contaminants un-derscores the imperative for developing novel cleanup methods that are efficient, economically viable, and that are intended to operate at high capacity and under continuous flows at the in-dustrial scale. This study shows the results of the operational design to build a prototype for the retention at lab scale of pollutants residues in water by using as adsorbent material, insoluble polymers prepared by β-cyclodextrin and epichlorohydrin as a cross-linking agent. Laboratory in batch tests were run to find out the adsorbent performances against furosemide and hydro-chlorothiazide as pollutants model. The initial evaluation concerning the dosage of adsorbent, pH levels, agitation, and the concentration of pharmaceutical pollutants enabled us to identify the optimal conditions for conducting the subsequent experiments. The adsorption kinetic and the mechanisms involved were evaluated revealing that that the experimental data perfectly fit the pseudo second order model being the adsorption process mainly governed by chemisorption. According to the KF constants values of 0.044 (L/g) and 0.029 (L/g) for furosemide and hydro-chlorothiazide, respectively and determination coefficient (R2) higher than 0.9 for both com-pounds, Freundlich yielded the most favorable outcomes, suggesting that the adsorption process occurs on heterogeneous surfaces involving both chemisorption and physisorption processes. The maximum monolayer adsorption capacity (qmax) obtained by Langmuir isotherm reveal a saturation of the β-CDs-EPI polymer surface 1.45 times higher for furosemide (qmax = 1.282 mg/g) than hydrochlorothiazide (qmax = 0.844 mg/g). Based on these results, the sizing design and building of a lab scale model were conducted, which in turn will be used later to evaluate its performances working in continuous flow in a real scenario.

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high le-thality and new therapeutics are needed as well as new spontaneous animal models to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors which share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and in rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, of its active metabolite berberrubine, and of eight analogues, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogues on cell viability, via induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction of CTGF expres-sion. Particularly the berberine analogues NAX035 and NAX057 show the highest therapeutic efficacy, de-serving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spon-taneous neoplastic diseases aiming at improving veterinary treatments of cancer as well as translational cancer research.

Background In many African countries, clinical samples are not routinely tested for carbapenem-resistant bacteria, the resistance data remaining limited. Material and methods In March 2020 –June 2022, we collected extended spectrum β-lactamase (ESBL) -producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. The species were identified using API20E and ESBL production confirmed by double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results Among the 473 ESBL-PE, 356 were ESBL- E. coli (ESBL-Ec) and 117 Klebsiella spp. (ESBL-K). Of the isolates, 5.3% were carbapenemase and 5.3% AmpC-β-lactamase positive Three types of carbapenemases were identified: 19 NDM, 3 OXA-48 like and 1 VIM. Two isolates produced both NDM and OXA48-like carbapenemases. Carbapenemase rates were highest among isolates in tertiary hospitals. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol, Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusion Many ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases, at all healthcare levels and in various samples, with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, vigorous resistance surveillance system, and infection control within healthcare.

The β-thalassemias are hereditary monogenic diseases characterized by low or absent production of adult hemoglobin and excess in the content of α-globin. This excess is cytotoxic for the erythroid cells and responsible of the β-thalassemia associated ineffective erythropoiesis. Therefore, the decrease of α-globin excess is a relevant clinical effect for these patients and can be obtained by induction of fetal hemoglobin, by autophagy, or both. The in vivo effects of sirolimus (rapamycin) and analogues on induction of fetal hemoglobin (HbF) is of key importance for therapeutic protocols in a variety of hemoglobinopathies, including β-thalassemia. In this research communication, we report data showing that decrease of autophagy-associated p62 protein, increased expression of ULK-1 and reduction of the excess of α-globin is operating in erythroid precursors (ErPCs) stimulated in vitro with low dosages of sirolimus. In addition, increased ULK-1 mRNA content and decrease of α-globin content were found in ErPCs isolated from β-thalassemia patients recruited for the NCT03877809 clinical trial and treated with 0.5-2 mg/day sirolimus. Our data support the concept that autophagy, ULK1 expression and α-globin chain reduction should be considered important endpoints in sirolimus-based clinical trials for β-thalassemia.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

Background: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β -Lapachone, a novel synthetic compound. Methods: The antibacterial activity of the β -Lapachone compound was examined against laboratory strains by agar well diffusion method, minimal inhibitory concentration (MICs), and minimal bactericidal concentration (MBCs). Growth kinetics inhibition in presence of β -Lapachone on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (ATCC 27853) was assessed by MABA. Crystal violet blue assay was used for biofilm inhibition assays, biofilm eradication assay and for molecular modeling PyMOL was used. Results: β -Lapachone exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Molecular modeling predicted the binding of β -Lap at active site and heme binding site of catalase, KatA. The activity of some commercial antibiotics was enhanced in association with β -Lap. In addition, β -Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains.

Klebsiella pneumoniae (Kp) has gained prominence in the last two decades due to its global spread as a multi-drug resistant (MDR) pathogen. Further, Carbapenem-Resistant Kp are emerging at an alarming rate. The objective of this study was (1) to evaluate the prevalence of β-lactamases, especially carbapenemases in Kp isolates from India, (2) determine the most prevalent sequence type (ST) & plasmids, and their association with β-lactamases. Clinical samples of K. pneumoniae (n=65) were collected from various pathology lab, drug susceptibility and minimum inhibitory concentrations (MIC) were detected. Whole genome sequencing (WGS) was done for (n=22) resistant isolates and WGS analysis was performed using various bioinformatics tools. Additional Indian MDR Kp genomes (n=187) were retrieved using Pathosystems Resource Integration Center (PATRIC) database. Detection of β-lactamase genes, location, plasmid replicons, and ST type of genomes were carried out using CARD, mlplasmids, PlasmidFinder, and PubMLST respectively. All data were analyzed and summarized using iTOL tool. ST231 was highest, followed by ST147, ST2096 & ST14 among Indian isolates. blaAmpH was detected as the most prevalent gene followed by blaCTX-M-15, blaTEM-1. Among carbapenemase genes, blaOXA-232 was prevalent and associated with ST231, ST2096 and ST14, which was followed by blaNDM-5 which was observed to prevalent in ST147, ST395 &ST437. ST231 genomes were most commonly found to carry Col440I and ColKP3 plasmids. ST16 carried mainly ColKP3, and Col (BS512) was abundantly present in ST147 genomes. One Kp isolate with novel MLST profile was identified, which carried blaCTX-M-15, blaOXA-1 and blaTEM-1. ST16 &ST14 from this study, which is mostly dual producer of carbapenem and ESBL genes, could be emerging high-risk clones in India.

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.

β-Ga2O3 crystal have attracted great attentions in the fields of photonics and photoelectronics because of its ultra wide-band gap and high thermal conductivity. Here, pure β-Ga2O3 crystal was successfully grown by optical floating zone (OFZ) method, and used as saturable absorbers to realize a passively Q-switched all-solid-state 1μm laser for the first time. By placing the as-grown β-Ga2O3 crystal into the resonator of Nd:GYAP solid-state laser, a Q-switched pulses at the center wavelength of 1080.4 nm are generated under a output coupling of 10%. The maximum output power is 191.5 mW while the shortest pulse width is 606.54 ns, and the maximum repetition frequency is 344.06 kHz. The maximum pulse energy and peak power are 0.567 μJ and 0.93 W, respectively. Our experimental results show that β-Ga2O3 crystal has great potential in the development of all-solid-state 1μm pulsed laser.

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjӧgren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS, although TGFβ family members seems to have ambiguous effects on the function of pSS salivary glands. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.