Search Results (25)

UV-cured methacrylated chitosan (MCHIT) hydrogels were achieved in the presence of silanised tellurium-doped silica bioactive glass (BG-Te-Sil) to produce an antimicrobial and osteoconductive scaffold for tissue engineering applications. Methacrylation of chitosan enabled efficient crosslinking, and the curing process was evaluated by means of Fourier-transform infrared spectroscopy (FTIR) and photorheology analyses. Compressive testing on crosslinked hydrogels showed that the silanised, bioactive, doped glass increased the hydrogel’s elastic modulus by up to 200% compared to unreinforced controls. Antibacterial assays against Staphylococcus aureus ATCC 43300 revealed a significant (p < 0.05) reduction in bacterial metabolic activity for hydrogels containing 50 wt% of the Te-doped bioactive glass. In vitro cytocompatibility with human bone-marrow mesenchymal stem cells demonstrated sustained viability and uniform distribution at 72 h (live/dead staining, AlamarBlue). Under H₂O₂-induced oxidative stress, reinforced hydrogels downregulated pro-inflammatory genes (TNF-α, IFN-γ, IL-1β, and PGES-2). These results suggest that the presence of the silanised bioactive glass can significantly enhance mechanical stability, antibacterial properties, and anti-inflammatory responses without affecting cytocompatibility, making these hydrogels promising for tissue engineering applications. Full article

Garlic (Allium sativum L.) is well known for its numerous health benefits; however, its strong flavor and aroma may limit its consumption due to gastrointestinal discomfort. This study aimed to evaluate puffing as a novel garlic processing method and compare the properties of puffed garlic with those of raw and black garlic (BG). Puffing was applied at different pressures after adjusting moisture content, resulting in significant physicochemical changes, including increased browning and the development of a porous, crunchy texture. In contrast, BG exhibited a black coloration and a gelatinous texture. Puffing resulted in a marked improvement in extraction yield (except at 196 kPa) and an increase in Maillard reaction products (MRPs), which correlated with the intensity of browning. Although the total phenolic content (TPC) and total flavonoid content (TFC) increased three-fold and eight-fold, respectively, compared to raw garlic, the antioxidant activities determined by DPPH and ABTS radical scavenging activities increased by 22-fold and 61-fold, respectively, compared to raw garlic. All garlic samples demonstrated anti-inflammatory activity, with puffing pressure significantly influencing the suppression of IL-6 production. While BG is widely recognized for its enhanced health-promoting properties, puffed garlic exhibited comparable antioxidant and anti-inflammatory benefits in a shorter time frame and with a better retention of garlic’s original flavor. These findings highlight puffing as an efficient and promising alternative to traditional garlic processing, enhancing functionality while reducing sensory drawbacks. Full article

This study evaluated short-term immune responses of dairy ewes supplemented with barley β-glucan (BG) following an intramammary Escherichia coli lipopolysaccharide (LPS) challenge. In the adaptation period, 36 ewes were fed an alfalfa hay diet ad libitum and barley grain cv. Hispanic (3.8% BG). Then, ewes were assigned into three experimental groups: (1) Control (CON), the same previous diet (13.3 g BG/d); (2) high β-glucans barley (HBG), new barley (cv. Annapurna) containing 10% BG (35 g BG/d); (3) intraperitoneally injected (INP) with a 1.4% BG solution dose (2 g BG/ewe). At d 9, all ewes were infused with an E. coli LPS or saline solution in each udder half. After the challenge, rectal temperature (RT), milk yield and composition, somatic cell count (SCC), and plasma interleukins (IL-1α and IL-1β) were monitored daily. The INP treatment revealed a transitory increase in RT and decreased milk yield by 38%. Milk fat, protein, and SCC increased in LPS-treated udders but not by BG treatment. The IL-1α plasma concentration was similar among groups but INP ewes showed a lower IL-1β concentration suggesting a lower inflammatory response. The BG administration appears more effective intraperitoneally than orally, which needs additional study. Full article

Strategies to increase the anti-tumor efficacy of cytokine-induced killer cells (CIKs) include genetic modification with chimeric antigen receptors (CARs) or the addition of soluble T-cell engaging bispecific antibodies (BsAbs). Here, CIKs were modified using a transposon system integrating two distinct anti-CD19 CARs (CAR-MNZ and CAR-BG2) or combined with soluble CD3xCD19 BsAb blinatumomab (CIK + Blina). CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah^®), carrying the 4-1BB and CD3ζ signaling elements, were employed. After transfection and CIK expansion, cells expressed CAR-CD19 to a similar extent (35.9% CAR-MNZ and 17.7% CAR-BG2). In vitro evaluations demonstrated robust proliferation and cytotoxicity (~50% cytotoxicity) of CARCIK-MNZ, CARCIK-BG2, and CIK + Blina against CD19⁺ target cells, suggesting similar efficacy. All effectors formed an increased number of synapses, activated NFAT and NFkB, and secreted IL-2 and IFN-ɣ upon encountering targets. CIK + Blina displayed strongest NFAT and IFN-ɣ induction, whereas CARCIK-BG2 demonstrated superior synapse formation. All the effectors have shown therapeutic activity in vivo against the CD19⁺ Daudi tumor model, with CARCIK cells showing a more durable response compared to CIK + Blina, likely due to the short half-life of Blina in this model. Full article

The non-specific protective effects offered by the concept of “innate immune memory” might represent a promising strategy to tackle early-life threatening infections. Here we tested the potential of an in vitro selected β-glucan in inducing trained immunity using an in vivo porcine model. We assessed the leukocyte transcriptome using blood transcriptomic module (BTM), proinflammatory cytokines, and clinical scoring after a first “training” and a second “stimulation” phase. The possible induction of innate immune memory was tested during a “stimulation” by an LPS-adjuvanted Mycoplasma hyopneumoniae vaccine (Hyogen^®) one day after weaning. Following the “training”, no major group differences were found, with the exception of a plasma TNF that was only induced by Adj and Adj_BG treatment. After vaccination, all groups developed similar antibody responses. A significant induction of plasma TNF and IL-1β was found in groups that received Adj and Adj_BG. However, following vaccination, the expected early innate BTMs were only induced by the PBS group. In conclusion, the adjuvant alone, adjuvant-formulated β-glucan, or orally applied β-glucan were unable to enhance innate immune reactivity but rather appeared to promote innate immune tolerance. Such an immune status could have both positive and negative implications during this phase of the piglet’s life. Full article

β-glucans found in cereal grains have been previously demonstrated to improve blood glucose control; however, current understanding points to their high viscosity as the primary mechanism of action. In this work, we present a novel, highly soluble, low-viscosity β-glucan fiber (HS-BG fiber) and a preclinical dataset that demonstrates its impact on two mechanisms related to the prevention of hyperglycemia. Our results show that HS-BG inhibits the activity of two key proteins involved in glucose metabolism, the α-glucosidase enzyme and the SGLT1 transporter, thereby having the potential to slow starch digestion and subsequent glucose uptake. Furthermore, we demonstrate in a multi-donor fecal fermentation model that HS-BG is metabolized by several different members of the gut microbiome, producing high amounts of short-chain fatty acids (SCFAs), known agonists of GPR43 receptors in the gut related to GLP-1 secretion. The production of SCFAs was verified in the translational gut model, SHIME^®. Moreover, HS-BG fiber fermentation produces compounds that restored permeability in disrupted epithelial cells, decreased inflammatory chemokines (CXCL10, MCP-1, and IL-8), and increased anti-inflammatory marker (IL-10), which could improve insulin resistance. Together, these data suggest that the novel HS-BG fiber is a promising new functional ingredient that can be used to modulate postprandial glycemic responses while the high solubility and low viscosity enable easy formulation in both beverage and solid food matrices. Full article

Goats belong to a group of animals called small ruminants and are critical sources of livelihood for rural people. Genomic sequencing can provide information ranging from basic knowledge about goat diversity and evolutionary processes that shape genomes to functional information about genes/genomic regions. In this study, we exploited a whole-genome sequencing data set to analyze the genetic diversity, population structure and selection signatures of 44 individuals belonging to 5 Ethiopian goat populations: 12 Aberegalle (AB), 5 Afar (AF), 11 Begait (BG), 12 Central highlands (CH) and 5 Meafure (MR) goats. Our results revealed the highest genetic diversity in the BG goat population compared to the other goat populations. The pairwise genetic differentiation (F_ST) among the populations varied and ranged from 0.011 to 0.182, with the closest pairwise value (0.003) observed between the AB and CH goats and a distant correlation (F_ST = 0.182) between the BG and AB goats, indicating low to moderate genetic differentiation. Phylogenetic tree, ADMIXTURE and principal component analyses revealed a classification of the five Ethiopian goat breeds in accordance with their geographic distribution. We also found three top genomic regions that were detected under selection on chromosomes 2, 5 and 13. Moreover, this study identified different candidate genes related to milk characteristics (GLYCAM1 and SRC), carcass (ZNF385B, BMP-7, PDE1B, PPP1R1A, FTO and MYOT) and adaptive and immune response genes (MAPK13, MAPK14, SCN7A, IL12A, EST1 DEFB116 and DEFB119). In conclusion, this information could be helpful for understanding the genetic diversity and population structure and selection scanning of these important indigenous goats for future genetic improvement and/or as an intervention mechanism. Full article

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions. Full article

The use of MAPLE synthesized thin films based on BG and VD3 for improving the osseointegration and corrosion protection of Ti-like implant surfaces is reported. The distribution of chemical elements and functional groups was shown by FTIR spectrometry; the stoichiometry and chemical functional integrity of thin films after MAPLE deposition was preserved, optimal results being revealed especially for the BG+VD3_025 samples. The morphology and topography were examined by SEM and AFM, and revealed surfaces with many irregularities, favoring a good adhesion of cells. The thin films’ cytotoxicity and biocompatibility were evaluated in vitro at the morphological, biochemical, and molecular level. Following incubation with HDF cells, BG57+VD3_ 025 thin films showed the best degree of biocompatibility, as illustrated by the viability assay values. According to the LDH investigation, all tested samples had higher values compared to the unstimulated cells. The evaluation of cell morphology was performed by fluorescence microscopy following cultivation of HDF cells on the obtained thin films. The cultivation of HDF’s on the thin films did not induce major cellular changes. Cells cultured on the BG57+VD3_025 sample had similar morphology to that of unstimulated control cells. The inflammatory profile of human cells cultured on thin films obtained by MAPLE was analyzed by the ELISA technique. It was observed that the thin films did not change the pro- and anti-inflammatory profile of the HDF cells, the IL-6 and IL-10 levels being similar to those of the control sample. The wettability of the MAPLE thin films was investigated by the sessile drop method. A contact angle of 54.65° was measured for the sample coated with BG57+VD3_025. Electrochemical impedance spectroscopy gave a valuable insight into the electrochemical reactions occurring on the surface. Full article

Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF. Full article

Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS–BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut. Full article

The purpose of this study was to evaluate the effect of 8-week β-alanine supplementation on C-Reactive Protein (CRP), interleukin-6 (IL-6), body composition, and bio-motor abilities in elite male basketball players. Twenty male basketball players (age: 23 + 0.6 years; body mass: 78.3 + 4.8 kg; height:185.3 + 5.4 cm, %BF, 15.2 ± 4.8) volunteered to participate in this study. They were divided into a β-alanine group (BG, N = 10) and a placebo group (PG, N = 10). All players were preparing for university competitions and had played for over five years. Players used 6.4 g/d of β-alanine in BG and maltodextrin in PG. The participants were involved in regular basketball training three months before the study. CRP, IL-6, body composition parameters, and bio-motor abilities were measured before starting the exercises and after completing the eight-week training period. The research findings showed a significant decrease in CRP and IL-6 and an increase in anaerobic peak power between the pre-test and post-test, as well as between BG and PG groups (p < 0.05). Although the other measured factors were a relative improvement compared to the pre-test and also compared to PG, these changes were not statistically significant (p < 0.05). Eight weeks of β-alanine supplementation ameliorated increases in IL-6 and CRP associated with in-season physical stressors in collegiate basketball players. These changes in pro-inflammatory cytokines suggest that β-alanine supplementation may be a useful nutritional strategy for immune regulation and can also improve anaerobic performance compared to PG. Full article

This study investigates the attenuating effects of butyrate glycerides (BG) on intestinal inflammatory responses and barrier dysfunction induced by LPS stimulation. An initial dose-response test was carried out to identify the optimal dose of BG for further testing. The mice were given intragastric administration of BG at different doses followed by lipopolysaccharide (LPS) intraperitoneal injection. The small intestinal morphology and cytokine mRNA expression were measured. With 1.5 g/kg BW BG administration, it was possible to alleviate the injury of duodenal morphology, attenuate ileum villus height reduction and promote IL-10 mRNA expression. Therefore, the optimal dosage of 1.5 g/kg BW BG was selected for the main experiment. The ultrastructure image of jejunum and ileum epithelial cells, mRNA expression, the level of cytokine and immunofluorescence in the ileum were analyzed. The results showed that BG maintain the ileac brush border, tight junction structures and protein expression. BG attenuated the increased inflammatory cytokines, TLR4 and JNK mRNA expression. Taken together, 1.5 g/kg BW BG administration maintained intestinal barrier function and reduced intestinal and body inflammation responses induced by LPS in mice. The mechanism by which BG alleviated intestinal inflammatory response and maintained intestinal barrier function may be related to the JNK signaling pathway. Full article

Previous studies found that melatonin modulates a combination of green-and-blue-light-induced B-lymphocyte proliferation via its membrane receptors Mel1a and Mel1c. However, in addition to its membrane-bound receptors, melatonin also functions through binding to nuclear receptors RORα/RORβ/RORγ. In this study, we raised 120 chicks under 400–700 nm white (WW), 660 nm red (RR), 560 nm green (GG) and 480 nm blue light (BB) from P0 to P26. From P27 to P42, half of the chickens in green, blue and red were switched to blue (G→B), green (B→G) and red (R→B), respectively. We used immunohistochemistry, Western blotting, qRT-PCR, Elisa and MTT to investigate the influence of various monochromatic light combinations on the bursal B lymphocyte apoptosis and oxidative stress levels as well as estimate whether melatonin and its nuclear receptors were involved in this process. Consistent with the increase in the plasma melatonin concentration and antioxidant enzyme activity, we observed that G→B significantly decreased the RORα, RORγ mRNA level, inhibited Bax, Caspase-3 and p-iκb, p-p65 protein expression, increased the IL-10 level and Nrf2, HO-1 protein expression, down-regulated the MDA and pro-inflammatory IL-6, TNF-α and IFN-γ levels in the bursa compared with WW, RR, GG, BB and R→B, respectively. Our in vitro results showed exogenous melatonin supplementation inhibited B-lymphocyte apoptosis, decreased IL-6, TNF-α, IFN-γ and ROS production, down-regulated RORα, RORγ mRNA level and p-iκb and p-p65 protein expression, whereas it improved the IL-10 level and Nrf2 and the HO-1 protein expression in bursal B lymphocyte. Moreover, these responses were abrogated by RORα agonist SR1078 but were mimicked by RORα antagonist SR3335 or RORγ antagonist GSK2981278. In addition, p65 antagonist BAY reversed RORα/RORγ-mediated G→B-inhibited bursal B lymphocyte apoptosis. Overall, we concluded that melatonin nuclear RORα/RORγ mediates G→B-inhibited bursal B lymphocyte apoptosis via reducing oxidative stress and Nfκb expression. Full article

(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman–DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial. Full article