Total Activity Research Articles

Paricalcitol attenuates oxidative stress and inflammatory response in the liver of NAFLD rats by regulating FOXO3a and NFκB acetylation

The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1β, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.

Artificial neural networks (ANN)-genetic algorithm (GA) optimization on thermosonicated achocha juice: kinetic and thermodynamic perspectives of retained phytocompounds

The extraction of phytocompounds from Achocha (Cyclanthera pedata) vegetable juice using traditional methods often results in suboptimal yields and efficiency. This study aimed to enhance the extraction process through the application of thermosonication (TS). To achieve this, an artificial neural network (ANN) and a genetic algorithm (GA) were utilized to simulate and optimize the process parameters. The study investigated the influence of ultrasonic amplitude (30%–50%), temperature (30 °C–50 °C), and sonication duration (15–60 min) on total polyphenolic content (TPC), total flavonoid content (TFC), antioxidant activity (AOA), and ascorbic acid content (AA). Remarkably, the ANN-GA optimization resulted in optimal TS conditions: an ultrasonic amplitude of 40%, a temperature of 40 °C, and a sonication duration of 30 min. Subsequent analysis of extraction kinetics and thermodynamics across various temperatures (30 °C–50 °C) and extraction times (0–30 min) demonstrated R 2 (0.98821) and χ2 (1.74773) for TPC with activation energy (Ea) 26.0456, R 2 (0.99906) and χ2 (0.07215) for TFC with Ea 26.2336, R 2 (0.99867) and χ2 (0.03003) for AOA with Ea 26.0987, R 2 (0.99731) and χ2 (0.13719) for AA with Ea 26.0984, validating the pseudo second-order kinetic model. These findings indicate that increased temperature enhances the saturation concentration and rate constant of phytochemical extraction.

Effectiveness of behavioural interventions with motivational interviewing on physical activity outcomes in adults: systematic review and meta-analysis

ObjectiveTo evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults.DesignSystematic review and meta-analysis.Study selectionA search of seven databases for randomised controlled trials published...

Effectiveness of behavioural interventions with motivational interviewing on physical activity outcomes in adults: systematic review and meta-analysis

ObjectiveTo evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults.DesignSystematic review and meta-analysis.Study selectionA search of seven databases for randomised controlled trials published...

Effects of tea infusion on selenium uptake in grapevine

Increased selenium (Se) content in fruits can supply Se in human body, but the effects of teas on the Se uptake in fruit trees are unknown. The effects of infusions of four teas (green, black, dark, and white) on the Se uptake of grapevine were studied to promote the Se uptake in fruit trees in this study. However, only black tea infusion increased the biomass, photosynthetic pigment content, superoxide dismutase (SOD) activity, peroxidase (POD) activity, and soluble protein content of grapevine. Except for white tea infusion, other tea infusions also increased the catalase (CAT) activity of grapevine. Furthermore, the tea infusions increased the activities of adenosine triphosphate sulfurase (ATPS) and adenosine 5’-phosphosulfate reductase (APR), and decreased the activities of serine acetyltransferase (SAT) and selenocysteine methyltransferase (SMT). Only the dark and white tea infusions increased the shoot total Se content by 86.53% and 23.32%, respectively (compared with the control), and also increased the shoot inorganic Se content and shoot organic Se content. Notably, four tea infusions decreased the organic Se proportion and increased the inorganic Se proportion in grapevine. Correlation and grey relational analyses showed that the root total Se content, ATPS activity, and ARP activity were closely associated with the shoot total Se content. The principal component and cluster analyses also showed that the ATPS activity, APR activity, root total Se content, and shoot total Se content were classified into one category. These findings show that black tea infusion can promote grapevine growth, while dark and white tea infusions can promote the Se uptake in grapevine.

A supersymmetric quantum perspective on the explicit large deviations for reversible Markov jump processes, with applications to pure and random spin chains

The large deviations at various levels that are explicit for Markov jump processes satisfying detailed balance are revisited in terms of the supersymmetric quantum Hamiltonian H that can be obtained from the Markov generator via a similarity transformation. We first focus on the large deviations at level 2 for the empirical density p^(C) of the configurations C seen during a trajectory over the large time window [0,T] , and rewrite the explicit Donsker–Varadhan rate function as the matrix element I[2][p^(.)]=⟨p^|H|p^⟩ involving the square-root ket |p^⟩ . (The analog formula is also discussed for reversible diffusion processes as a comparison.) We then consider the explicit rate functions at higher levels, in particular for the joint probability of the empirical density p^(C) and the empirical local activities a^(C,C′) characterizing the density of jumps between two configurations (C,C′) . Finally, the explicit rate function for the joint probability of the empirical density p^(C) and of the empirical total activity A^ that represents the total density of jumps of a long trajectory is written in terms of the two matrix elements ⟨p^|H|p^⟩ and ⟨p^|Hoff|p^⟩ , where Hoff represents the off-diagonal part of the supersymmetric Hamiltonian H. This general framework is then applied to pure or random spin chains with single-spin-flip or two-spin-flip transition rates, where the supersymmetric Hamiltonian H corresponds to quantum spin chains with local interactions involving Pauli matrices of two or three neighboring sites. It is then useful to introduce the quantum density matrix ρ^=|p^⟩⟨p^| associated with the empirical density p^(.) in order to rewrite the various rate functions in terms of reduced density matrices involving only two or three neighboring sites.

Optimization of supercritical CO2 fluid extraction process, component analysis, and antioxidant spectral activity correlation of Huoluo Xiaoling Dan

ABSTRACT This study elucidated the optimization conditions, GC-MS analysis conditions, total antioxidant activity, and components closely related to antioxidant activity for supercritical extraction of active ingredients in Huoluo Xiaoling Dan (HLXLD). The yield, octyl acetate content, and total antioxidant activity of HLXLD under different conditions were obtained through orthogonal experiments, and the optimal supercritical extraction conditions were determined to be 45°C, 25 MPa, and 4 h. The supercritical extract was subjected to GC-MS analysis and matched with the WILEY and NIST databases, resulting in the qualitative identification of 37 chemical components with a matching degree above 60. The similarity evaluation system of traditional Chinese medicine fingerprint was used to evaluate all orthogonal experimental samples, with a similarity ranging from 0.522 to 0.989. Thirteen common characteristic peaks were selected, and the quantification of these peaks was performed using peak area normalization method. The combination of the content of common characteristic peaks in different samples and their total antioxidant activity was analyzed using multivariate statistical methods such as principal component analysis and multiple regression equation. It was found that five components, F3, F2, F5, F7 and F12, among the common characteristic peaks were closely related to antioxidant activity.

In vitro bioactivities and shelf life protective properties of sumac extracts against foodborne pathogens and computational analysis of sumac compounds

The aim of this study was to investigate the antibacterial, antibiofilm, antioxidant and shelf life protective potentials of infusion, decoction, and room temperature samples of sumac fruits prepared as used by the local people against three foodborne pathogens including Bacillus cereus, Escherichia coli O157:H7, and Staphylococcus aureus isolated from food samples. The room temperature samples of sumac showed a remarkable antibacterial activity (81.25%) against S. aureus. Infusion and decoction samples of sumac fruit showed an effective antibacterial activity (∼70%) against E. coli O157:H7. Moderate efficacy against B. cereus was observed in all treatment groups. Antibiofilm effects of sumac were observed against B. cereus and S. aureus, but not against E. coli O157:H7. The total antioxidant activity was found to be close to the reference compounds. The twenty-two phenolic and flavonoid chemical compounds (gallic acid, gentisic acid, protocatechuic acid, protocatechualdehyde, 4-OH-benzoic acid, salicylic acid, chlorogenic acid, cafeic acid, p-coumaric acid, ferulic acid, rosmarinic acid, sinapic acid, trans-cinnamic acid, rutin, resveratrol, myricetin, naringenin, quercetin, luteolin, kaempferol, apigenin, and chrysin) were identified by Liquid Chromatography Mass Spectrometer (LC-MS/MS) and these molecules were analyzed by computational analyses using SwissADME, admetSAR 3.0 and the AntiBac-Pred web tool. In addition, the antibacterial efficacy of sumac fruit extracts was tested on mixed Mediterranean salad samples to evaluate the shelf-life enhancing effect. The efficacy of sumac fruit against common foodborne pathogens suggests that the ethnobotanical use of sumac may provide protection against bacterial diseases and can be utilized as an additive and/or ingredient in the food industry.

Effect of microwave roasting on chemical and bioactive compounds of pistachio (Pistacia vera L.) kernels

SummaryIn the present study, the effect of microwave roasting on the total phenolic quantities, antioxidant activities, phenolic constituents, fatty acids and tocopherol amounts of the pistachio kernel and oil was revealed. The moisture, oil, total phenolic amounts and antioxidant capacity value of raw and roasted pistachio nuts were assessed as 31.13%, 28.58%, 34.79 mgGAE/100 g and 0.75%–3.18%, 56.91%, 18.80 mgGAE/100 g and 2.26%, respectively. The raw pistachio nut contains 1.90 gallic acid, 0.22 3,4‐dihydroxybenzoic acid, 0.87 (+)‐catechin, 0.15 1,2‐dihydroxybenzene, 0.15 rutin trihydrate, 0.16 resveratrol, 0.1 quercetin, 0.19 kaempferol and 0.24 mg/100 g isorhamnetin. In addition, microwave‐roasted nuts contained 0.75 gallic acid, 0.62 3,4‐dihydroxybenzoic acid, 0.83 (+)‐catechin, 0.47 1,2‐dihydroxybenzene, 0.21 syringic acid, 0.17 caffeic acid and 0.17 mg/100 g quercetin. The raw and roasted pistachio nut oils contained 74.12% and 71.16% oleic, 13.76% and 15.23% linoleic, 8.16% and 8.92% palmitic and 2.09% and 2.10% stearic acids, respectively. The oil samples of the raw and roasted kernels contained 8.15 and 0.00 α‐tocopherol, 63.78 and 7.60 β‐tocopherol, 8.72 and 7.40 ɣ‐tocopherol and 5.61 and 6.77 mg g−1 δ‐tocopherols, respectively. The total phenolic quantity of the pistachio kernel roasted by microwave decreased significantly. Phenolic compounds of the pistachio kernel showed partial differences depending on microwave heating. Differences were monitored in the fatty acid profiles of Pistachio kernel oils. β‐tocopherol quantity of the oil of the pistachio kernel heated by microwave significantly decreased.

Effect of microwave roasting on chemical and bioactive compounds of pistachio (Pistacia vera L.) kernels

SummaryIn the present study, the effect of microwave roasting on the total phenolic quantities, antioxidant activities, phenolic constituents, fatty acids and tocopherol amounts of the pistachio kernel and oil was revealed. The moisture, oil, total phenolic amounts and antioxidant capacity value of raw and roasted pistachio nuts were assessed as 31.13%, 28.58%, 34.79 mgGAE/100 g and 0.75%–3.18%, 56.91%, 18.80 mgGAE/100 g and 2.26%, respectively. The raw pistachio nut contains 1.90 gallic acid, 0.22 3,4‐dihydroxybenzoic acid, 0.87 (+)‐catechin, 0.15 1,2‐dihydroxybenzene, 0.15 rutin trihydrate, 0.16 resveratrol, 0.1 quercetin, 0.19 kaempferol and 0.24 mg/100 g isorhamnetin. In addition, microwave‐roasted nuts contained 0.75 gallic acid, 0.62 3,4‐dihydroxybenzoic acid, 0.83 (+)‐catechin, 0.47 1,2‐dihydroxybenzene, 0.21 syringic acid, 0.17 caffeic acid and 0.17 mg/100 g quercetin. The raw and roasted pistachio nut oils contained 74.12% and 71.16% oleic, 13.76% and 15.23% linoleic, 8.16% and 8.92% palmitic and 2.09% and 2.10% stearic acids, respectively. The oil samples of the raw and roasted kernels contained 8.15 and 0.00 α‐tocopherol, 63.78 and 7.60 β‐tocopherol, 8.72 and 7.40 ɣ‐tocopherol and 5.61 and 6.77 mg g−1 δ‐tocopherols, respectively. The total phenolic quantity of the pistachio kernel roasted by microwave decreased significantly. Phenolic compounds of the pistachio kernel showed partial differences depending on microwave heating. Differences were monitored in the fatty acid profiles of Pistachio kernel oils. β‐tocopherol quantity of the oil of the pistachio kernel heated by microwave significantly decreased.

The Discovery, Molecular Cloning, and Characterization of Dextransucrase LmDexA and Its Active Truncated Mutant from Leuconostoc mesenteroides NN710.

Dextransucrases play a crucial role in the production of dextran from economical sucrose; therefore, there is a pressing demand to explore novel dextransucrases with better performance. This study characterized a dextransucrase enzyme, LmDexA, which was identified from the Leuconostoc mesenteroides NN710. This bacterium was isolated from the soil of growing dragon fruit in Guangxi province, China. We successfully constructed six different N-terminal truncated variants through sequential analysis. Additionally, a truncated variant, ΔN190LmDexA, was constructed by removing the 190 amino acids fragment from the N-terminal. This truncated variant was then successfully expressed heterologously in Escherichia coli and purified. The purified ΔN190LmDexA demonstrated optimal hydrolysis activity at a pH of 5.6 and a temperature of 30 °C. Its maximum specific activity was measured to be 126.13 U/mg, with a Km of 13.7 mM. Results demonstrated a significant improvement in the heterologous expression level and total enzyme activity of ΔN190LmDexA. ΔN190LmDexA exhibited both hydrolytic and transsaccharolytic enzymatic activities. When sucrose was used as the substrate, it primarily produced high-molecular-weight dextran (>400 kDa). However, upon the addition of maltose as a receptor, it resulted in the production of a significant amount of oligosaccharides. Our results can provide valuable information for enhancing the characteristics of recombinant dextransucrase and potentially converting sucrose into high-value-added dextran and oligosaccharides.

Effects of Foliar Dressing with Chemical Nano-Selenum and Na2SeO3 on the Antioxidant System and Accumulation of Se and Bioactive Components in Cyclocarya paliurus (Sweet Tea Tree)

Selenium (Se)-rich Cyclocarya paliurus is popular for its bioactive components, and exogenous Se fortification is the most effective means of enrichment. However, the effects of exogenous Se fortification on the nutritional quality of C. paliurus are not well known. To investigate the nutrient contents and antioxidant properties of C. paliurus following Se treatment, we used a foliar spray to apply Se in two forms—chemical nano-Se (Che-SeNPs) and sodium selenite (Na2SeO3). Sampling began 10 days after spraying and was conducted every 5 days until day 30. The Se, secondary metabolite, malondialdehyde contents, antioxidant enzyme activity, Se speciation, and Se-metabolism-related gene expression patterns were analyzed in the collected samples. Exogenous Se enhancement effectively increased the Se content of leaves, reaching a maximum on days 10 and 15 of sampling, while the contents of flavonoids, triterpenes, and polyphenols increased significantly during the same period. In addition, the application of Se significantly enhanced total antioxidant activity, especially the activity of the antioxidant enzyme peroxidase. Furthermore, a positive correlation between the alleviation of lipid peroxidation and Se content was observed, while methylselenocysteine formation was an effective means of alleviating Se stress. Finally, Na2SeO3 exhibited better absorption and conversion efficiency than Che-SeNPs in C. paliurus.

Effects of Foliar Dressing with Chemical Nano-Selenum and Na2SeO3 on the Antioxidant System and Accumulation of Se and Bioactive Components in Cyclocarya paliurus (Sweet Tea Tree).

Selenium (Se)-rich Cyclocarya paliurus is popular for its bioactive components, and exogenous Se fortification is the most effective means of enrichment. However, the effects of exogenous Se fortification on the nutritional quality of C. paliurus are not well known. To investigate the nutrient contents and antioxidant properties of C. paliurus following Se treatment, we used a foliar spray to apply Se in two forms-chemical nano-Se (Che-SeNPs) and sodium selenite (Na2SeO3). Sampling began 10 days after spraying and was conducted every 5 days until day 30. The Se, secondary metabolite, malondialdehyde contents, antioxidant enzyme activity, Se speciation, and Se-metabolism-related gene expression patterns were analyzed in the collected samples. Exogenous Se enhancement effectively increased the Se content of leaves, reaching a maximum on days 10 and 15 of sampling, while the contents of flavonoids, triterpenes, and polyphenols increased significantly during the same period. In addition, the application of Se significantly enhanced total antioxidant activity, especially the activity of the antioxidant enzyme peroxidase. Furthermore, a positive correlation between the alleviation of lipid peroxidation and Se content was observed, while methylselenocysteine formation was an effective means of alleviating Se stress. Finally, Na2SeO3 exhibited better absorption and conversion efficiency than Che-SeNPs in C. paliurus.

Assessment of Encapsulated Probiotic Lactococcus lactis A12 Viability Using an In Vitro Digestion Model for Tilapia.

Probiotics face harsh conditions during their transit through the gastrointestinal tract (GIT) of fish because of low-pH environments and intestine fluid. Therefore, the evaluation of probiotic viability under simulated gastrointestinal conditions is an important step to consider for probiotic supplementation in fish feed prior to in vivo trials. Therefore, this study aimed to evaluate the effect of stomach and intestinal simulated conditions on the viability of encapsulated Lactococcus lactis A12 using an in vitro digestion model for tilapia. A Box Behnken design was used to evaluate the potential effect of three factors, namely stomach pH, residence time in the stomach, and enzyme quantity, on the viability of encapsulated Lactococcus lactis A12. As the main results, low pH (4.00), long residence time (4 h), and enzyme quantity (2.68 U of total protease activity) led to lower final cell counts after the phases of the stomach and intestine. Encapsulated probiotic bacteria showed higher viability (p < 0.05) and antibacterial activity (p < 0.05) against the pathogen Streptococcus agalactiae than non-encapsulated bacteria. The results suggest that L. lactis A12 survives in GIT conditions and that the proposed in vitro model could be used to explore the viability of probiotic bacteria intended for fish feed supplementation.

Determination Of Total Phenolic And Antioxidant Activity Of Wild Cherry Tomatoes – Solanum Peruvianum: Sample From Awang Sekmai, Manipur.

Objective: An investigation was carried out to assess the total phenolic, antioxidant characteristics, antioxidant components, and antioxidant enzyme activity in developed cherry tomato breeding lines at the point of harvest when the tomatoes are completely mature and have turned red in colour.

Изучение некоторых функциональных характеристик ферментативных гидролизатов пищевых белков

Food allergy is a matter of global concern, proteins being a popular allergen worldwide. Enzymatic protein hydrolysates serve as hypoallergenic components in functional foods. This article describes enzymatic hydrolysates of egg and soy proteins as potential antigens, sensitizers, and antioxidants. The research featured soy protein isolate and egg albumin. The protein hydrolysates were obtained in a two-step process with pepsin and trypsin to measure hydrolysis, total antioxidant activity, and residual antigenicity. The sensitizing ability of native proteins and their hydrolysates was studied using a delayed-type hypersensitivity (DTH) skin test of paw swelling in mice. The egg albumin and soy protein were hydrolyzed by sequentially adding the proteases, i.e., pepsin and trypsin. The degree of protein hydrolysis was calculated against total nitrogen and its contents in non-hydrolyzed raw materials and hydrolysate. It was 82.6% for the egg hydrolysate and 88.3% for the soy hydrolysate, the total antioxidant activity being 114.3 and 91.4 mg/100 mL, respectively. The residual antigenicity of the hydrolysates determined by ELISA in a sandwich version was 1.55×10–4 and 3.30×10–4 RU, respectively. The native egg and soy proteins demonstrated good allergenic properties, and the DTH response index increased fivefold. The hydrolysates reduced the DTH response indices by an average of 3.5 for egg hydrolysate and 2.6 times for soy hydrolysate. The resulting enzymatic hydrolysates of egg albumin and soy protein demonstrated a high degree of hydrolysis and antioxidant activity. They had low residual antigenicity (10–4) and low sensitizing ability. The resulting enzymatic hydrolysates could be used as hypoallergenic components and antioxidants in new functional foods.

Gamma irradiation as a method to enhance antioxidant activity and inhibit rancidification of brown rice

Brown rice is a nutrient-rich alternative to white rice, but its higher lipid content makes it prone to rancidification. This study investigated the impact of gamma irradiation on the antioxidant activity and rancidification of brown rice. The results revealed that irradiation at doses of 5 and 10 kGy significantly increased the total phenolic content and radical scavenging activity of SL-218 brown rice. Exposure to 5 kGy of gamma radiation led to a 7.23% decrease in the free fatty acid (FFA) content compared to the control, as confirmed by Fourier-transform infrared spectroscopy analysis. Long-term storage studies using SL-7 and RC-160 brown rice varieties at lower doses (0.5 and 1 kGy) validated the reduction in FFA content. These findings highlight the potential of gamma irradiation to enhance the quality of brown rice by effectively reducing FFA content and improving its antioxidant activity.

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia.

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish.

Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1H NMR and 13C NMR mass (ESI+) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1, 3, PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10, with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research.

Long-Term Impact of Nutritional Intervention with Increased Polyphenol Intake and Physical Activity Promotion on Oxidative and Inflammatory Profiles in Patients with Metabolic Syndrome.

Obesity and overweight pose significant risks to health, contributing to the prevalence of chronic conditions like type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). The current study aimed to assess the impact of a 6-year nutritional and lifestyle intervention on oxidative and inflammatory markers in individuals aged 55 to 75, specifically those at high risk of CVD. A study was carried out in a group of 80 participants with metabolic syndrome (MetS) residing in Mallorca, Spain, who underwent nutritional intervention based on a low-calorie Mediterranean diet (MedDiet) and promotion of physical activity. Before and after the intervention, several parameters including anthropometric data, haematological factors, blood pressure, and physical activity level were measured. Oxidative and inflammatory biomarkers in plasma were analysed. After the 6-year intervention, participants who managed to reduce their body mass index (BMI) had greater reductions in abdominal obesity, waist to heigh ratio (WHtR), diastolic blood pressure, and glucose levels, and increased high density protein cholesterol (HDL-c) compared to those who did not reduce BMI. This higher reduction in BMI was related to reduced energy intake and increased adherence to MedDiet, with greater polyphenol intake, and total physical activity (PA). Furthermore, improvements in oxidative stress and proinflammatory status were observed in participants who reduced their BMI. Significant reductions in the activity of the prooxidant enzyme, myeloperoxidase (MPO), levels of the lipid oxidation marker, malondialdehyde (MDA), and the proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1,) were found in those who reduced their BMI. In contrast, participants who did not improve their BMI exhibited higher levels of proinflammatory markers such as MCP-1 and tumour necrosis factor α (TNFα), as well as increased activity of the antioxidant enzyme catalase (CAT). Current findings suggest that an effective way to reduce BMI is a hypocaloric MedDiet combined with tailored physical activity to improve oxidative stress and proinflammatory status, and potentially reducing the risk of CVD.