Search Results (18)

Background: Lung cancer is the leading cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) as the most common subtype. Dysbiotic intratumoral mycobiomes drive LUAD pathogenesis, and Aspergillus sydowii (A. sydowii) acts as a key oncogenic fungal species. Ginseng polysaccharides (GPs), bioactive phytochemicals with immunomodulatory and oncostatic properties, counteract fungal infections and restore immunosurveillance in LUAD. Methods: Subcutaneous and orthotopic LUAD murine models were established by implanting Lewis lung carcinoma (LLC) cells. Subcutaneous tumors were infected intratumorally and orthotopic models via nasal inoculation. GPs (200 mg/kg/day) were orally administered to evaluate tumor growth. Metagenomic and targeted bile acid metabolomic profiling of fecal and tumor tissues was performed, with Spearman correlations analyzed using R packages. Results: GPs significantly inhibited A. sydowii-induced tumor growth in both models. In subcutaneous tumors; GPs reduced volume (p < 0.05) and weight vs. infected controls. In orthotopic models, GPs decreased pathological nodules and lung weight, with micro-CT/H&E confirming attenuated hyperplasia. Metagenomics showed GPs restored gut homeostasis by enriching Lactobacillus/Muribaculum intestinale and suppressing pro-inflammatory Alistipes. Targeted metabolomics revealed reduced β-Hyodeoxycholic Acid (3β-HDCA), Chenodeoxycholic acid 24-acyl-b-D-glucuronide (CDCA-24G) and 3β-hydroxychol-5-en-24-oic acid (5-isoLCA) after GP treatment. Network analysis confirmed significant microbe–bile acid interactions. Conclusions: GPs exert antitumor effects against A. sydowii-induced LUAD by modulating gut microbiota and bile acid metabolism. This identifies GPs as a promising therapy for mycobiome-influenced cancers, with dual targeting of fungal infection and metabolic reprogramming. Full article

The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of Lactobacillus and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism. Full article

Background: Traumatic hemorrhage and infection are major causes of mortality in wounds caused by battlefield injuries, hospital procedures, and traffic accidents. Developing a multifunctional nano-drug capable of simultaneously controlling bleeding, preventing infection, and promoting wound healing is critical. This study aimed to design and evaluate a nanoparticle-based solution to address these challenges effectively. Methods: Using a one-pot assembly approach, we prepared a series of nanoparticles composed of poly-L-lysine and hyodeoxycholic acid (PLL-HDCA NPs). Theoretical simulations and experimental studies were combined to optimize their structure and functionality. In vitro platelet aggregation, antibacterial assays, cytotoxicity tests, and hemolysis evaluations were performed. In vivo efficacy was assessed in various hemorrhage models, a full-thickness skin defect model, and a skin irritation test. Results: PLL-HDCA NPs demonstrated effective induction of platelet aggregation and significantly reduced bleeding time and blood loss in mouse models, including tail vein, femoral vein, artery, and liver bleeding. Antibacterial assays revealed strong activity against E. coli and S. aureus. Wound healing studies showed that PLL-HDCA NPs promoted tissue repair in a full-thickness skin defect model. Cytotoxicity and hemolysis tests indicated minimal impact on human cells and significantly reduced hemolysis rates compared to PLL alone. Skin irritation tests confirmed the safety of PLL-HDCA NPs for external application. Conclusions: PLL-HDCA NPs represent a safe, efficient, and multifunctional nano-drug suitable for topical applications to control bleeding, combat infection, and facilitate wound healing, making them promising candidates for use in battlefield and hospital settings. Full article

This study aimed to investigate the effects of bile acids (BAs) supplementation on fatty liver hemorrhagic syndrome (FLHS), production performance, and physiological and quality characteristics of laying hen eggs. Sixty Sanhuang laying hens, aged 28 weeks, were randomly allocated to six dietary treatments over a 4-week period, including the control (CON) group (feeding basal diet), the high-fat diet (HFD)-treated group (basal diet containing 10% soybean oil), and HFD supplemented with 0.01% and 0.02% of chenodeoxycholic acid (CDCA) or hyodeoxycholic acid (HDCA) groups. Production performance, egg quality, liver morphology, serum biochemical indexes, antioxidant capacity, proinflammatory cytokines, and intestinal microbiota were evaluated. The average body weight in 0.01% CDCA was larger than in the HFD group (p < 0.05). Eggshell Thickness in the CON group was greater than in the HFD, 0.01% CDCA, and HDCA groups (p < 0.05). Albumen height in the 0.02% HDCA group was higher than the HFD group (p < 0.05). Eggshell weight in the HFD group was less than the CON group (p < 0.05). Haugh unit (HU) in the HDCA group was larger than the HFD group (p < 0.05). Albumen weight in the 0.02% HDCA group was greater than the CON and HFD groups (p < 0.05). In the HFD group, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipo-protein cholesterol (LDL-C) were surpassing the other groups (p < 0.05). The levels of catalase (CAT) and total superoxide dismutase (T-SOD) in the HFD group was smaller than the other groups (p < 0.05). The level of malondialdehyde (MDA) in the HFD group was higher than in the other groups (p < 0.05). Tumor necrosis factor-α (TNF-α) levels were larger in the HFD group than in the other groups (p < 0.05). The 16S rRNA sequencing analysis indicated significant variations in the relative abundance of specific bacterial populations among the different treatment groups. The treatment and CON groups exhibited a higher presence of bacteria that inhibit host energy absorption or promote intestinal health such as Firmicutes, Bacteroidetes, and Ruminococcus, whereas the HFD group showed an increased prevalence of potentially pathogenic or deleterious bacteria, such as Desulfovibrio spp. In conclusion, the supplementation of BAs in poultry feed has been demonstrated to effectively mitigate the detrimental effects of FLHS in laying hens. This intervention regulates lipid metabolism, bolsters antioxidant defenses, reduces inflammation, and modulates the gut microbiota, offering a novel perspective on the application of BAs in the poultry industry. Full article

Viili, a Finnish ropy fermented milk, is traditionally manufactured through spontaneous fermentation, by mesophilic lactic acid bacteria and yeast-like fungi, or back-slopping. This study evaluated four natural viili starters as sources of lactic acid bacteria for dairy production. Back-slopping activation of the studied viili samples was monitored through pH and titratable acidity measurements and enumeration of mesophilic lactic acid bacteria. Sixty lactic acid bacteria isolates were collected, molecularly identified, and assayed for acidification performance, enzymatic activities, production of exopolysaccharides (EPSs), presence of the histidine decarboxylase (hdcA) gene of Gram-positive bacteria, and production of bacteriocins. A neat predominance of Lactococcus lactis emerged among the isolates, followed by Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus lactis, and Lactococcus cremoris. Most isolates exhibited proteolytic activity, whereas only a few enterococci showed lipase activity. Five isolates identified as L. cremoris, L. lactis, and E. faecalis showed a good acidification performance. Most of the isolates tested positive for leucine arylamidase, whereas only one E. durans and two L. lactis isolates were positive for valine arylamidase. A few isolates also showed a positive reaction for beta-galactosidase and alpha- and beta-glucosidase. None of the isolates produced EPSs or bacteriocins. The hdcA gene was detected in five isolates identified as L. lactis and E. faecium. A few L. cremoris and L. lactis isolates for potential use as starter or adjunct cultures for dairy processing were finally identified. Full article

Background: Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression. Methods: Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6. Results: The PD-L1 tumor proportion score (TPS) was higher, while the immune cell score (IC-score) was lower in the more aggressive TET subtypes and in more advanced Masaoka–Koga stages. A positive correlation between PD-L1 and HDAC-3, -4, and -5 cytoplasmic expression was identified. Conclusions: Higher PD-L1 expression in neoplastic cells and lower PD-L1 expression in immune cells of TETs characterizes more aggressive and advanced neoplasms. Correlations between PD-L1 and HDAC expression unravel the impact of epigenetic regulation on the expression of immune checkpoint molecules in TETs, with possible future applications in combined therapeutic targeting. Full article

Histone deacetylase 6 (HDAC6), by deacetylation of multiple substrates and association with interacting proteins, regulates many physiological processes that are involved in cancer development and invasiveness such as cell proliferation, apoptosis, motility, epithelial to mesenchymal transition, and angiogenesis. Due to its ability to remove misfolded proteins, induce autophagy, and regulate unfolded protein response, HDAC6 plays a protective role in responses to stress and enables tumor cell survival. The scope of this review is to discuss the roles of HDCA6 and its implications for the therapy of colorectal cancer (CRC). As HDAC6 is overexpressed in CRC, correlates with poor disease prognosis, and is not essential for normal mammalian development, it represents a good therapeutic target. Selective inhibition of HDAC6 impairs growth and progression without inducing major adverse events in experimental animals. In CRC, HDAC6 inhibitors have shown the potential to reduce tumor progression and enhance the therapeutic effect of other drugs. As HDAC6 is involved in the regulation of immune responses, HDAC6 inhibitors have shown the potential to improve antitumor immunity by increasing the immunogenicity of tumor cells, augmenting immune cell activity, and alleviating immunosuppression in the tumor microenvironment. Therefore, HDAC6 inhibitors may represent promising candidates to improve the effect of and overcome resistance to immunotherapy. Full article

Gut microorganisms are involved in the development and severity of different cardiovascular diseases, and increasing evidence has indicated that dietary fibre and polyphenols can interact with the intestinal microbiota. The study objective was to investigate the effect of onion and apple intake on the major types of microbial-derived molecules, such as short-chain fatty acids (SCFAs) and bile acids (BAs). Obese Zucker rats were randomly assigned (n = eight rats/group) to a standard diet (OC), a standard diet/10% onion (OO), or a standard diet/10% apple (OA). Lean Zucker rats fed a standard diet served as a lean control (LC) group. Faecal samples were collected at baseline, and 8 weeks later, the composition of the microbial community was measured, and BA and SCFA levels were determined using high-performance liquid chromatography–mass spectrometry (HPLC-MS) and gas chromatography–mass spectrometry (GC-MS), respectively. Rats fed onion- and apple-enriched diets had increased abundance of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus spp., enhanced SCFAs (acetic, propionic, isobutyric, and valeric acids), decreased excretion of some BAs, mainly of the primary (CA, α-MCA, and β-MCA) and secondary type (ω-MCA, HDCA, NCA, DCA, and LCA), and increased amount of taurine- and glycine-conjugated BAs compared to the OC group. The contribution of specific bioactive compounds and their metabolites in the regulation of the microbiome and the pathways linked to SCFA and BA formation and their relationship with some diseases needs further research. Full article

Metformin is a first-line drug for the clinical treatment of type 2 diabetes; however, it always leads to gastrointestinal tolerance, low bioavailability, short half-life, etc. Liposome acts as an excellent delivery system that could reduce drug side effects and promote bioavailability. Hyodeoxycholic acid, a cholesterol-like structure, can regulate glucose homeostasis and reduce the blood glucose levels. As an anti-diabetic active ingredient, hyodeoxycholic acid modifies liposomes to make it overcome the disadvantages of metformin as well as enhance the hypoglycemic effect. By adapting the thin-film dispersion method, three types of liposomes with different proportions of hyodeoxycholic acid and metformin were prepared (HDCA:ME-(0.5:1)-Lips, HDCA:ME-(1:1)-Lips, and HDCA:ME-(2:1)-Lips). Further, the liposomes were characterized, and the anti-type 2 diabetes activity of liposomes was evaluated. The results from this study indicated that three types of liposomes exhibited different characteristics—Excessive hyodeoxycholic acid decreased encapsulation efficiency and drug loading. In the in vivo experiments, liposomes could reduce the fasting blood glucose levels, improve glucose tolerance, regulate oxidative stress markers and protect liver tissue in type 2 diabetic mice. These results indicated that HDCA:ME-(1:1)-Lips was the most effective among the three types of liposomes prepared and showed better effects than metformin. Hyodeoxycholic acid can enhance the hypoglycemic effect of metformin and play a suitable role as an excipient in the liposome. Full article

Ventricina del Vastese is a traditional dry fermented sausage from Central Italy not yet characterized for the occurrence, identity and safety of coagulase-negative staphylococci (CNS), a bacterial group technologically important for this kind of product. Therefore, in this study, 98 CNS isolates from four manufacturers were differentiated using repetitive element palindromic PCR (Rep-PCR) and identified using 16S rRNA gene sequencing. These were examined for genes encoding biogenic amine (BA) production, resistance to aminoglycosides, β-lactams, tetracyclines and staphylococcal enterotoxins (SEs). Staphylococcus succinus (55%) predominated, followed by S. xylosus (30%), S. epidermidis (7.4%), S. equorum (3.1%), S. saprophyticus (3.1%) and S. warneri (1%). One S. succinus subsp. casei isolate was slightly β-hemolytic. SEs and the histidine decarboxylase gene hdcA were not detected, whereas the tyrosine decarboxylase gene tdcA was detected in four S. xylosus isolates. The blaZ beta-lactamase gene in an S. equorum isolate, tetracycline resistance genes tetK in six S. succinus isolates and tetA in one S. succinus isolate also bearing tetK were found. The product examined is characterized by a peculiar CNS species ratio and a low occurrence and diversity of AR transferable genes than found in other studies, as a probable consequence of production only with meat from animals raised in small farms with extensive rearing systems in which antibiotic usage is infrequent. Full article

This investigation is motivated by increasing interest in diamond and composite films for applications in biomedical and electronic devices. A biomimetic strategy is based on the use of commercial bile acids, such as ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA). Composite films are developed using UDCA and HDCA as solubilizing agents for poly(ethyl methacrylate) (PEMA) in isopropanol and as dispersing agents for micro- and nanodiamonds. In this approach, the use of traditional toxic solvents for PEMA dissolution is avoided. The ability to obtain high concentrations of high molecular mass PEMA and disperse diamond particles in such solutions is a key factor for the development of a dip-coating method. The PEMA dissolution and diamond dispersion mechanisms are discussed. The composition and microstructure of the films can be varied by variation of the diamond particle size and concentration in the suspensions. The films can be obtained as singular layers of different compositions, multilayers of similar composition, or alternating layers of different compositions. The films combine corrosion protection property and biocompatibility of PEMA with advanced functional properties of diamonds. Full article

Characterization of the molecular mechanisms involved in tumor cell clustering could open the way to new therapeutic strategies. Towards this aim, we used an in vitro quantitative procedure to monitor the anchorage-independent cell aggregation kinetics in a panel of 25 cancer cell lines. The analysis of the relationship between selected aggregation dynamic parameters and the gene expression data for these cell lines from the CCLE database allowed identifying genes with expression significantly associated with aggregation parameter variations. Comparison of these transcripts with the perturbagen signatures from the Connectivity Map resource highlighted that they were strongly correlated with the transcriptional signature of most histone deacetylase (HDAC) inhibitors. Experimental evaluation of two HDAC inhibitors (SAHA and ISOX) showed that they inhibited the initial step of in vitro tumor cell aggregation. This validates our findings and reinforces the potential interest of HDCA inhibitors to prevent metastasis spreading. Full article

Here, we explored the influences of thyme microcapsules on the growth, gene expression, and histamine accumulation by Proteus bacillus isolated from smoked horsemeat sausage. RT-qPCR was employed to evaluate the gene expression level of histidine decarboxylase (HDC) cascade-associated genes. We used HPLC to monitor histamine concentration both in pure culture as well as in the processing of smoked horsemeat sausage. Results showed that histamine accumulation was suppressed by thyme microcapsule inhibitory effect on the histamine-producing bacteria and the reduction in the transcription of hdcA and hdcP genes. Besides, compared with thyme essential oil (EO), thyme microcapsules exhibited higher antibacterial activity and had a higher score for overall acceptance. Therefore, the addition of thyme microcapsules in Xinjiang smoked horsemeat sausage inhibits histamine accumulation. Full article

The aim of this work was to identify and characterize, from a technological and safety point of view, the lactic acid bacteria (LAB) isolated from traditional sheep-fermented sausage. First, LABs were identified then were screened for some technological parameters such as acidifying and growth ability, proteolytic and lipolytic activity and for antimicrobial activity. Finally, biogenic amine production and degradation abilities were also evaluated. This research reveals the predominance of Lactiplantibacillus (L.) plantarum on LAB community. Almost all L. plantarum strains were active against Listeria monocytogenes strains (inhibition zone diameters > 1 cm). None of the tested strains were positive in histidine (hdcA), lysine (ldc) and tyrosine (tyrdc) decarboxylase genes and only one (L. plantarum PT9-2) was positive to the agmatine deiminase (agdi) gene. Furthermore, given the positive results of the sufl (multi-copper oxidase) gene detection, all strains showed a potential degradation ability of biogenic amines. Full article

This study proposed a model for highway accident detection that combines the You Only Look Once v3 (YOLOv3) object detection algorithm and Canny edge detection algorithm. It not only detects whether an accident has occurred in front of a vehicle, but further performs a preliminary classification of the accident to determine its severity. First, this study established a dataset consisting of around 4500 images mainly taken from the angle of view of dashcams from an open-source online platform. The dataset was named the Highway Dashcam Car Accident for Classification System (HDCA-CS) and was developed with the aim of conforming to the setting of this study. The HDCA-CS not only considers weather conditions (rainy days, foggy days, nighttime settings, and other low-visibility conditions), but also various types of accidents, thus increasing the diversity of the dataset. In addition, we proposed two types of accidents—accidents involving damaged cars and accidents involving overturned cars—and developed three different design methods for comparing vehicles involved in accidents involving damaged cars. Canny edge detection algorithm processed single high-resolution images of accidents were also added to compensate for the low volume of accident data, thereby addressing the problem of data imbalance for training purposes. Lastly, the results showed that the proposed model achieved a mean average precision (mAP) of 62.60% when applied to the HDCA-CS testing dataset. When comparing the proposed model with a benchmark model, two abovementioned accident types were combined to allow the proposed model to produce binary classification outputs (i.e., non-occurrence and occurrence of an accident). The HDCA-CS was then applied to the two models, and testing was conducted using single high-resolution images. At 76.42%, the mAP of the proposed model outperformed the benchmark model’s 75.18%; and if we were to apply the proposed model to only test scenarios in which an accident has occurred, its performance would be even better relative to the benchmark. Therefore, our findings demonstrate that our proposed model is superior to other existing models. Full article