Search Results (5,279)

In this study, the response surface method (RSM) was used to optimize the deproteinization process of polysaccharides from Vitis vinifera L. SuoSuo (VTP). The antioxidant capacities of polysaccharides before and after deproteinization were evaluated. The structure of deproteinized VTP (DVTP), which has relatively strong antioxidant activity, was characterized, and the protective effect of DVTP on H₂O₂-induced HT22 cell damage was evaluated. The results of the RSM experiment revealed that the ideal parameters for deproteinization included a chloroform/n-butanol ratio (v/v) of 4.6:1, a polysaccharide/Sevage reagent (v/v) ratio of 2:1, a shaking time of 25 min, and five rounds of deproteinization. Preliminary characterization revealed that the DVTP was an acidic heteropolysaccharide composed of seven monosaccharides, among which the molar ratio of galacturonic acid was 40.65. FT-IR and the determination of uronic acid content revealed that DVTP contained abundant uronic acid and that the content was greater than that of VTP. In vitro, the antioxidant activity assay revealed that the hydroxyl radical scavenging capacity and total antioxidant capacity of DVTP were greater than those of VTP. In the range of 0.6~0.8 mg/mL, the DPPH scavenging capacities of VTP and DVTP were greater than that of vitamin C. In addition, cell viability was measured via a CCK-8 assay, which revealed that DVTP had a strong defense effect on H₂O₂-induced damage to HT22 cells. These findings suggest that DVTP has high antioxidant activity and could be used as a natural antioxidant in functional foods and medicines. Full article

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV–vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025–0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation. Full article

Background and Objectives: Remodeling and healing of the graft are crucial processes for long-term graft survival after anterior cruciate ligament reconstruction (ACLR). However, few studies have objectively evaluated the differences in graft healing between autografts and allografts. This study aimed to compare the status of the anterior cruciate ligament (ACL) grafts between hamstring tendon (HT) autografts and tibialis anterior tendon (TAT) allografts using second-look arthroscopy. Materials and Methods: The outcomes of 193 consecutive patients (153 males and 40 females, with an average age of 30.38 and BMI of 25.43 kg/m²) who underwent second-look arthroscopy following primary ACLR were retrospectively reviewed. Prior to participating in this study, all patients provided written informed consent. The patients were divided into two groups: those with HT autografts and those with TAT allografts. Confounding factors were matched between the two groups using propensity score matching (PSM). ACL graft status was assessed during second-look arthroscopy using a numeric scale system based on the degree of four parameters: graft tension, continuity, synovium coverage, and vascular marking. Clinical outcomes were assessed using the Lysholm and International Knee Documentation Committee (IKDC) scores. Graft status and clinical outcomes were compared between the two groups. Additionally, a subgroup analysis based on the timing of the second-look arthroscopy (12–24 months vs. >24 months after the initial ACLR) was conducted. Results: After PSM, 62 patients were included in each group. The second-look arthroscopy was conducted at 23.6 ± 6.6 months for the HT group and at 24.0 ± 7.9 months for the TAT group (p = 0.749). The continuity and tension of the ACL graft were not significantly different between the two groups (p = 0.146 and 0.075, respectively). However, the TAT group exhibited significantly inferior synovial coverage and vascular marking of the ACL graft compared with the HT group (p = 0.021 and 0.007, respectively). These findings were consistent regardless of the timing of the second-look arthroscopy. Clinical outcomes, according to the Lysholm and IKDC scores, significantly improved in both groups with no significant differences (p = 0.386 and 0.733, respectively). Conclusions: Although there were no differences in graft tension and continuity between HT autografts and TAT allografts, the biological healing of ACL grafts, in terms of synovialization and vascularization, was superior in HT autografts compared to TAT allografts. Full article

Background: Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. Methods: HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Results: Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D₁, optic chiasm D_max, optic nerves D_max, and p-cord D₁. IMPT showed advantages for oral cavity D_mean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. Conclusions: NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes. Full article

The study explored proteomics to better understand the relationship between type 2 diabetes (T2DM) and hypertension (HT) in Thai adults, using shotgun proteomics and bioinformatics analysis. Plasma samples were taken from 61 subjects: 14 healthy subjects (mean age = 40.85 ± 7.12), 13 with T2DM (mean age = 57.38 ± 6.03), 16 with HT (mean age = 66.87 ± 10.09), and 18 with coexisting T2DM/HT (mean age = 58.22 ± 10.65). Proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein–protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) version 11.5. We identified six unique proteins in T2DM patients, including translationally controlled 1 (TPT1) and nibrin (NBN), which are associated with the DNA damage response. In HT patients, seven unique proteins were identified, among them long-chain fatty acid-CoA ligase (ASCL), which functions in the stimulation of triacylglycerol and cholesterol synthesis, and NADPH oxidase activator 1 (NOXA1), which is involved in high blood pressure via angiotensin II-induced reactive oxygen species (ROS)-generating systems. In coexisting T2DM/HT patients, six unique proteins were identified, of which two—microtubule-associated protein 1A (MAP1A)—might be involved in dementia via RhoB-p53 and diacylglycerol kinase beta (DGKB), associated with lipid metabolism. This study identified new candidate proteins that are possibly involved in the pathology of these diseases. Full article

Background: Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration and death of retinal ganglion cells (RGCs), leading to blindness. Current glaucoma interventions reduce intraocular pressure but do not address retinal neurodegeneration. In this effort, to identify new pharmacological targets for glaucoma management, we employed a network pharmacology approach. Methods: We first retrieved transcriptomic data from GEO, an NCBI database, and carried out GEO2R (an interactive web tool aimed at comparing two or more groups of samples in a GEO dataset). The GEO2R statistical analysis aimed at identifying the top differentially expressed genes (DEGs) and used these as input of STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) app within Cytoscape software, which builds networks of proteins starting from input DEGs. Analyses of centrality metrics using Cytoscape were carried out to identify nodes (genes or proteins) involved in network stability. We also employed the web-server software MIRNET 2.0 to build miRNA–target interaction networks for a re-analysis of the GSE105269 dataset, which reports analyses of microRNA expressions. Results: The pharmacological targets, identified in silico through analyses of the centrality metrics carried out with Cytoscape, were rescored based on correlations with entries in the PubMed and clinicaltrials.gov databases. When there was no match (82 out of 135 identified central nodes, in 8 analyzed networks), targets were considered “potential innovative” targets for the treatment of glaucoma, after further validation studies. Conclusions: Several druggable targets, such as GPCRs (e.g., 5-hydroxytryptamine 5A (5-HT5A) and adenosine A_2B receptors) and enzymes (e.g., lactate dehydrogenase A or monoamine oxidase B), were found to be rescored as “potential innovative” pharmacological targets for glaucoma treatment. Full article

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT_1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented. Full article

Background: Heart transplantation (HT) remains the ultimate treatment for end-stage heart failure. An endomyocardial biopsy (EMB) is “the gold standard” diagnostic procedure used in HT rejection surveillance. The aim of this study is to provide a detailed analysis of the histopathological characteristics of the EMB and to investigate if there is a correlation between some histopathological changes, such as fibrosis, vasculitis, Quilty effect (Q.E.), myocytes damage, and the presence of episodes of acute rejection. Methods: In this retrospective study, 200 EMBs were included, coming from 65 patients transplanted in the Emergency Institute for Cardiovascular Diseases and Transplantation (ICvDT) Targu Mures between 2012 and 2024. Fibrosis, vasculitis, Q.E., myocyte damage, etc., were microscopically evaluated to see if these parameters correlate with rejection episodes. Results: The mean age was 38.18 years (SD 15.67), 25% of biopsies being recorded in the 41–50 age group. 77.14% of total acute cellular rejection (ACR) was of mild rejection, with most registered in the 11–20 age group; the cases of severe rejection being recorded in the 41–50 age group. Antibody-mediated rejection (AMR) was recorded more frequently in women with a representation of 23.4%, compared to 8.5% of men. 86.7% (39 cases) of the total number of EMBs with fibrosis score 3 and 71.4% (15 cases) of the total EMBs with fibrosis score 2 were recorded in men, compared to the 28.6% (6 cases) of fibrosis score 2 recorded in women (p = 0.013). 50.0% of all the EMB recorded in the 61–70 age group showed fibrosis score 3, compared to 34.8% of those from the 21–30 age group. The Q.E. was identified in 13% of the biopsies and, in some patients, it was observed across 3–4 successive biopsies. Mild vasculitis was associated in 34.9% of cases with ISHLT ≥ 1R and moderate vasculitis was associated in 87.5% of cases with ISHLT ≥ 1R. Conclusions: Fibrosis was detected much more frequently in men and in the 61–70 age group. In addition to the histopathological changes specific to acute rejection, there are other pathological changes, such as the Q.E., and vasculitis and myocytes damage and disarray, that seem to suggest a close connection with rejection, but extensive studies are needed to confirm this. Full article

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative properties. However, despite various clinical trials, scientific evidence regarding the impact on sleep of orally ingested GABA, whether natural or synthesized through biological pathways, is not clear. GABALAGEN (GBL) is the product of fermented collagen by Lactobacillus brevis BJ20 (L. brevis BJ20) and Lactobacillus plantarum BJ21 (L. plantarum BJ21), enriched with GABA and characterized by low molecular weight. The aim of this study was to investigate the effect of GBL on sleep improvement via a receptor binding assay in a pentobarbital-induced sleep-related rat model. We utilized a pentobarbital-induced sleep-related rat model to conduct this research. The present study investigated the sedative effects of GBL through electroencephalography (EEG) analysis in the pentobarbital-induced sleep animal model. Exploration of the neural basis of these positive effects involved evaluating orexin in the brain via immunohistochemical methods and 5-HT in the serum using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we conducted a binding assay for 5-HT_2C receptors, as these are considered pivotal targets in the mechanism of action for sleep aids. Diazepam (DZP) was used as a positive control to compare the efficacy of GBL. Results: In the binding assay, GBL displayed binding affinity to the 5-HT_2C receptor (IC50 value, 5.911 µg/mL). Administration of a low dose of GBL (GBL_L; 100 mg/kg) increased non-rapid eye movement sleep time and decreased wake time based on EEG data in pentobarbital-induced rats. Administration of a high dose of GBL (GBL_H; 250 mg/kg) increased non-rapid eye movement sleep time. Additionally, GBL groups significantly increased concentration of the 5-HT level in the serum. GBL_H decreased orexin expression in the lateral hypothalamus. Conclusion: Overall, the sedative effect of GBL may be linked to the activation of serotonergic systems, as indicated by the heightened affinity of the 5-HT_2C receptor binding and elevated levels of 5-HT observed in the serum. This suggests that GBL holds promise as a novel compound for inducing sleep in natural products. Full article

Though the mechanisms are not fully understood, tryptophan (Trp) and physical exercise seem to regulate mechanical hypersensitivity in fibromyalgia. Here, we tested the impact of Trp supplementation and continuous low-intensity aerobic exercise on the modulation of mechanical hypersensitivity in a fibromyalgia-like model induced by acid saline in female rats. Twelve-month-old female Wistar rats were randomly divided into groups: [control (n = 6); acid saline (n = 6); acid saline + exercise (n = 6); acid saline + Trp (n = 6); and acid saline + exercise + Trp (n = 6)]. Hypersensitivity was caused using two intramuscular jabs of acid saline (20 μL; pH 4.0; right gastrocnemius), 3 days apart. The tryptophan-supplemented diet contained 7.6 g/hg of Trp. The three-week exercise consisted of progressive (30–45 min) treadmill running at 50 to 60% intensity, five times (Monday to Friday) per week. We found that acid saline induced contralateral mechanical hypersensitivity without changing the levels of Trp, serotonin (5-HT), and kynurenine (KYN) in the brain. Hypersensitivity was reduced by exercise (~150%), Trp (~67%), and its combination (~160%). The Trp supplementation increased the levels of Trp and KYN in the brain, and the activity of indoleamine 2,3-dioxygenase (IDO), and decreased the ratio 5-HT:KYN. Exercise did not impact the assessed metabolites. Combining the treatments reduced neither hypersensitivity nor the levels of serotonin and Trp in the brain. In conclusion, mechanical hypersensitivity induced by acid saline in a fibromyalgia-like model in female rats is modulated by Trp supplementation, which increases IDO activity and leads to improved Trp metabolism via the KYN pathway. In contrast, physical exercise does not affect mechanical hypersensitivity through brain Trp metabolism via either the KYN or serotonin pathways. Because this is a short study, generalizing its findings warrants caution. Full article

Perry disease (PeD) is a rare, neurodegenerative, genetic disorder inherited in an autosomal dominant manner. The disease manifests as parkinsonism, with psychiatric symptoms on top, such as depression or sleep disorders, accompanied by unexpected weight loss, central hypoventilation, and aggregation of DNA-binding protein (TDP-43) in the brain. Due to the genetic cause, no causal treatment for PeD is currently available. The only way to improve the quality of life of patients is through symptomatic therapy. This work aims to review the latest data on potential PeD treatment, specifically from the medicinal chemistry and computer-aided drug design (CADD) points of view. We select proteins that might represent therapeutic targets for symptomatic treatment of the disease: monoamine oxidase B (MAO-B), serotonin transporter (SERT), dopamine D₂ (D₂R), and serotonin 5-HT_1A (5-HT_1AR) receptors. We report on compounds that may be potential hits to develop symptomatic therapies for PeD and related neurodegenerative diseases and relieve its symptoms. We use Phase pharmacophore modeling software (version 2023.08) implemented in Schrödinger Maestro as a ligand selection tool. For each of the chosen targets, based on the resolved protein–ligand structures deposited in the Protein Data Bank (PDB) database, pharmacophore models are proposed. We review novel, active compounds that might serve as either hits for further optimization or candidates for further phases of studies, leading to potential use in the treatment of PeD. Full article

Cattle productivity, whether in terms of meat yield or milk production, is intricately regulated by a multitude of factors. Among them, hormone concentrations play a significant role, reflecting the complex interplay between endocrine regulation and physiological processes that ultimately determine the efficiency and yield of production. High concentrations of 5-hydroxytriptamine (5-HT) are associated with a reduced metabolic load at the onset of lactation and a lower milk yield. Thyroid hormones (THs) and cortisol also affect several metabolic pathways, including carbohydrate, protein, and lipid metabolism. The aim of this study was to assess if milk or meat aptitudes and age influence circulating 5-HT, THs, and cortisol concentrations, investigating the possible interactions among these parameters. The research was performed on 46 healthy cows of three different breeds. Enzyme-linked immunosorbent assay (ELISA) methods were used to quantify circulating 5-HT and cortisol concentrations, and an immunochemiluminescent analyzer was used for THs. For parameters exhibiting non-normal distributions, an ANCOVA model using age, aptitude, and their interaction as fixed factors was applied. Significant lower T3 concentrations were recorded in dairy cows than in meat cows. Moreover, T4 significantly decreased with advancing age both in cows aimed at milk and meat production. Lastly, T4 was positively correlated with T3 and 5-HT in meat production-oriented cows. Full article

The aim of this study was to investigate the qualitative and quantitative fruit profiles of ten cultivars (cvs.) of haskap berry (Lonicera caerulea var. kamtschatica Sevast.) to determine their antioxidant activity (ABTS test, CUPRAC test, ability to capture superoxide (O₂˙⁻) and hydroxyl radicals (OH˙)), cytotoxic activity (against cancer cell lines breast, MCF-7; colon, HT-29; and melanoma, SK-Mel-28) and physicochemical properties. Most of the selected cultivars had not previously been analyzed for these properties. A total of 19 polyphenolic compounds were identified in the fruits of the tested genotypes, with a quantitative range of 2166.3–3597.0 µg/g. The polyphenol profile was dominated by anthocyanins (90.0–92.4%), and the remaining classes occurred in the following order: phenolic acids > flavonols > flavan-3-ols. The highest concentrations of these polyphenol groups were found in the cultivars ‘Honeybee’, ‘Sinij Uties’ and ‘Usłada’. The fruits of these cultivars were also characterized by the highest antioxidant activity (546.6–683.5 µg/mL for O₂˙⁻ and 541.2–652.1 µg/mL for OH˙) and cytotoxic activity (103.6–649.2 µg/mL). The data obtained indicate that the fruits of the new haskap cultivars are a good source of bioactive compounds with possible health-promoting properties. Full article

The consequences of heat stress during the dry period can extend into the postpartum period, affecting health and productivity in the subsequent lactation. We hypothesized that cows with distinct core body temperatures (CBTs) would exhibit disparate behaviors associated with different degrees of heat generation or dissipation. The primary objective was to investigate behavioral differences of dry Holstein cows (n = 50) classified as high-temperature (HT) or low-temperature (LT), based on median CBT during the summer months using visual observations and accelerometer technology. A secondary objective was to investigate the transcriptome of white blood cells (WBCs) collected from a subgroup of HT and LT cows (n = 5; per group). Minor behavior differences were observed during the visual observations (performed for a total of 16h/cow). Based on automated monitoring system (AMS) data, collected 24/7 over a period of 42 days per cow, HT cows displayed higher periods of high activity and lower periods of inactivity prepartum and diminished rumination time postpartum than LT cows. There were 16 differently expressed genes (DEGs) in WBCs of HT compared to LT cows. Several of the identified DEGs have been previously associated with heat stress. The observed trends in the AMS data indicate that CBT and patterns of activity prepartum may serve as valuable predictors for identifying dairy cows with distinct tolerance to heat stress. Full article

Accelerated synthesis of gold nanoparticles (AuNPs) in charged microdroplets produced by electrospray ionization (ESI) was exploited to modify the surface of graphite screen-printed electrodes (GSPEs). The deposited AuNPs were then functionalized by the charged microdroplets deposition of 6-ferrocenyl-hexanethiol (6Fc-ht) solutions that act as reducing and stabilizing agents and provide electrochemical properties for the modified electrodes. The morphology and composition of the AuNPs were characterized by scanning electron microscopy (SEM). Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were used to investigate the electrochemical behavior of the modified electrodes. The results showed that the ESI microdroplets deposition technique produces uniform and well-dispersed AuNPs on GSPE, and optimal conditions for deposition were identified, enhancing GSPE electrocatalytic performance. Further functionalization by ESI microdroplets of AuNPs with 6Fc-ht demonstrated improved redox properties compared with the conventional self-assembled monolayer (SAM) method, highlighting the technique’s potential for the easy and fast functionalization of electrochemical sensors. Full article