Search Results (33,038)

Lysozyme is an enzyme that hydrolyzes bacterial cell walls, which is functional for destroying the integrity of bacteria, enhancing the activity of immune cells, participating in immune signal transmission, helping to maintain the micro-ecological balance of the gastrointestinal tract, etc. Egg white lysozyme (EWL), as one of the typical representatives of lysozyme, is the most widely used enzyme in production so far, and is also one of the most complex structures of lysozyme. EWL also helps protect plants from fungal and bacterial diseases. Here, we report the effect of EWL on infections from plant viruses. The EWL gene was cloned and characterized. The EWL protein sequence analysis identified a conserved domain of lysozyme activity and the sharing of a 100% identical EWL protein from the Coturnix japonica lysozyme. Then, the EWL gene was cloned into the plant expression vector pEAQ-HT-DEST3 and transiently expressed in Nicotiana benthamiana (N. benthamiana). We found that EWL expression in N. benthamiana significantly contributed to infections by the turnip mosaic virus (TuMV) but not by the tobacco mosaic virus (TMV). Plants that transiently expressed EWL showed an obvious increase in resistance to Botrytis cinerea (B.cinerea). Our results suggested a new research point for the application of EWL on plant pathogen infections. Full article

Introduction: Bell’s palsy is a common acute peripheral neurological disorder causing unilateral facial paralysis. Its exact etiology remains unknown, but it is linked to inflammation, immune responses, infections, and ischemia. This study explores the potential causal relationship between Bell’s palsy and peripheral blood inflammatory proteins, metabolites, and immune cell characteristics. Methods: Genetic data for Bell’s palsy were obtained from the Finnish database (version R10) and IEU OpenGWAS. A two-sample Mendelian randomization (MR) approach was applied, analyzing 4907 plasma proteins, 731 immune cell traits, 91 inflammatory proteins, and 1400 metabolites. The Finnish dataset served as the discovery cohort, while the IEU OpenGWAS dataset acted as the validation cohort. Bioinformatics analyses included protein–protein interaction (PPI) networks, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, colocalization, and Linkage Disequilibrium Score Regression (LDSC) to identify candidate proteins and explore potential therapeutic targets. Results: MR analysis identified 70 inflammatory proteins, 77 metabolites, and 26 immune cell traits as potentially causally associated with Bell’s palsy. After external validation, BLVRB, HMOX2, TNFRSF12A, DEFB128, ITM2A, VEGF-A, and DDX58 remained significantly associated (p < 0.05). PPI network analysis led to 31 candidate proteins, and six core proteins (JAK2, IL27RA, OSM, CCL19, SELL, VCAM-1) were identified. Conclusions: Our study identifies causal relationships between inflammatory proteins, metabolites, immune cells, and Bell’s palsy, highlighting that the JAK/STAT signaling pathway may be a potentially critical target for intervention in Bell’s palsy, and that its modulation may provide new directions and opportunities for therapeutic strategies and drug discovery for the disease. Full article

Background and Objectives: Stereotactic radiotherapy enhances local tumor control by delivering high doses directly to the tumor. It is thought to activate the immune system via T-cells, possibly creating a systemic response. This study aims to evaluate stereotactic body radiotherapy’s (SBRT) impact on the immune system by measuring T-cell transcription factors, such as TBX21, GATA-3, FoxP3, and RORɣt. Materials and Methods: Peripheral blood samples were collected from 103 patients before SBRT and from 66 patients two months post-treatment. We measured transcription factors TBX21, GATA-3, FOXP3, and RORγt using ELISA, and performed a complete blood count and C-reactive protein analysis to rule out infections. Statistical analyses included paired t-tests and correlation analyses to assess changes before and after treatment. Results: Post-treatment, significant reductions were observed in TBX21 (Th1), GATA-3 (Th2), and FOXP3 (Treg), while RORɣt (Th17) remained stable but trended higher in lung cancer patients. No correlations were found with demographic factors. However, TBX21 levels were significantly related to the planning target volume (PTV) and biologically effective dose (BED10) in the lung region. Larger PTVs (≥16.5 cc) and higher BED10 doses (≥100 Gy) were linked to smaller reductions in TBX21 (p = 0.008, p = 0.04) and increased RORɣt levels (p = 0.01). Conclusions: Stereotactic radiotherapy reduces immunosuppressive markers like FOXP3 and GATA-3, indicating its potential to boost immune activation by suppressing Treg and Th2 cells. Larger target volumes and higher BED10 values may enhance Th1 responses through TBX21. These findings suggest that SBRT activates the immune system, and its combination with immunotherapy could be promising. Full article

Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and Grassland-Thoroughbreds (CY), we conducted histological and bioinformatic analyses on the gluteus medius muscle of these three horse breeds. Immunofluorescence analysis revealed that Grassland-Thoroughbreds had the highest proportion of fast-twitch muscle fibers at 78.63%, while Mongolian horses had the lowest proportion at 57.54%. Whole-transcriptome analysis identified 105 differentially expressed genes (DEGs) in the CY vs. MG comparison and 104 DEGs in the CY vs. XL comparison. Time-series expression profiling grouped the DEGs into eight gene sets, with three sets showing significantly up-regulated or down-regulated expression patterns (p < 0.05). Additionally, 280 differentially expressed long non-coding RNAs (DELs) were identified in CY vs. MG, and 213 DELs were identified in CY vs. XL. A total of 32 differentially expressed microRNAs (DEMIRs) were identified in CY vs. MG, while 44 DEMIRs were found in CY vs. XL. Functional enrichment analysis indicated that the DEGs were significantly enriched in essential biological processes, such as actin filament organization, muscle contraction, and protein phosphorylation. KEGG pathway analysis showed their involvement in key signaling pathways, including the mTOR signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. Furthermore, functional variation-based analyses revealed associations between non-coding RNAs and mRNAs, with some non-coding RNAs targeting genes potentially related to muscle function regulation. These findings provide valuable insights into the molecular basis for the environmental adaptability, athletic performance, and muscle characteristics in horses, offering new perspectives for the breeding of Grassland-Thoroughbreds. Full article

Little is known about the effect of hepatic hemangiomas on protein induced by vitamin K absence or antagonist II (PIVKA-II). The aim of this study was to clarify the correlation of PIVKA-II levels with hepatic hemangiomas. In 335 consecutive patients with hepatic hemangiomas, ultrasonography (US), laboratory tests for liver function, serum levels of PIVKA-II and α-fetoprotein (AFP), and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin–antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDPs)) as indicators of coagulation disorders were examined. PIVKA-II levels were significantly higher in the hemangioma group than in the control group (p < 0.0001), and significantly higher in the large hemangioma group (p < 0.0001). PIVKA-II levels in the hemangioma increase group were higher with increases in tumor size and abnormal coagulation factors, and those in the hemangioma decrease group were lower with decreases in tumor size and abnormal coagulation factors. PIVKA-II levels were significantly correlated with tumor size (p < 0.0001) and all coagulation factors (p < 0.05) except prothrombin. Hepatic hemangiomas were associated with elevated serum PIVKA-II levels, showing significant correlations with tumor size and coagulation disorders. PIVKA-II elevation was attributed to the increased production of prothrombin precursors caused by accelerated coagulation–fibrinolysis within hemangiomas. Full article

Phaeodactylum tricornutum is rich in bioactive substances, rendering it valuable in nutrition and medicine. Epigenetic editing mediated by human RNA demethylase FTO can significantly increase the yields of rice and potato and offers significant potential for the genetic breeding of microalgae. This study aimed to enhance the production of certain metabolites in P. tricornutum via FTO-mediated epigenetic editing. Phenotypic analysis revealed that transgenic P. tricornutum exhibits significantly reduced RNA m⁶A modification levels and faster growth, producing markedly higher levels of lipids, proteins, and carotenoids than the wild type. Transcriptome analysis revealed 1009 upregulated genes and 378 downregulated genes. KEGG analysis demonstrated the upregulated expression of multiple key enzymes involved in long-chain fatty acid synthesis (e.g., ACSL, fabF, and fabG), carotenoid synthesis (e.g., crtQ, PDS, and PSY1), and amino acid synthesis (e.g., dapF, glyA, and aroK) in transgenic P. tricornutum, consistent with our phenotypic results. These results indicate that FTO can promote growth and increase the bioactive compound content in P. tricornutum by regulating the m⁶A modification of RNA, and further suggest that FTO has the potential to serve as a new tool for the epigenetic editing of microalgae. Full article

Natural pigments like betacyanins are highly unstable under heat, light, acid, and alkaline conditions. Yeast protein (YP) is a promising substitute protein, while chitooligosaccharides (COS) are water-soluble alkaline polysaccharides. Water-in-oil-in-water (W₁/O/W₂) emulsions, with two-membrane, three-phase structure, can serve as effective carriers for stabilizing pigments. In this study, YP-COS complexes formed through electrostatic interactions were used as hydrophilic emulsifiers to create betacyanin-coated W₁/O/W₂ emulsions. The W₁/O colostrum was designed to make up 30%, 70%, and 90% of the emulsion (v/v)and the W₂ was designed by the complexes with three concentrations of YP (2%, 1.25% and 0.5%, w/v)-COS (6%, 3.75% and 1.5%, w/v). The optimal formulation was determined through comprehensive evaluation of micromorphological characteristics, particle size, zeta potential and creaming index, ultimately yielding a system comprising YP (2%)-COS (6%) and 90% W₁/O colostrum. Moreover, the W₁/O/W₂ emulsion system significantly improved the betacyanins retention under thermal treatment, photolytic exposure, pH gradients, and extended storage compared to the betacyanin aqueous solution (p < 0.05). In vitro digestion tests showed the emulsion retained 58.39% of betacyanins, while the betacyanin aqueous solution retained only 41.42%, demonstrating the emulsion’s ability to delay the betacyanins release, offering new insights for using YP-COS complexes in food production and other fields. Full article

The effect of various natural antioxidants—grape seed extract (GSE), ascorbic acid (AA), α-tocopherol (TP), a combination of GSE and AA, and a combination of GSE and TP—on pH, water activity, color change, lipid oxidation, antioxidant capacity, total bacterial count, protein content and free fatty acids was studied in sausages during the drying process. The model sausage system was prepared according to a traditional Bulgarian recipe for “lukanka”. AA and KNO₃ were used in the recipe as antioxidants and preservatives, respectively. The results obtained with natural antioxidants were compared with the results of samples prepared according to the traditional recipe and with a synthetic antioxidant, butylated hydroxytoluene. The samples with a combination of GSE and AA showed the highest antilipid potential, the lowest malondialdehyde values (0.41 mg/kg MDA), the highest antimicrobial capacity (TBC 78.50 × 10³ cfu/g), the lowest color change, and the lowest change in antioxidant activity (17.74%), through the sausage drying process. There was an obviously synergistic effect between GSE and AA, and their antioxidant activity was highly effective. The sample with 0.05% GSE ranked second. The samples with a synthetic antioxidant and a combination of KNO₃ and AA gave similar results, but KNO₃ had a toxic effect. The samples with α-tocopherol had lower results. It was found that grape seed extracts and the combination of GSE and AA were the most effective and could successfully replace synthetic antioxidants, improve the quality of sausages, and provide healthier foods to consumers. Full article

The BCS1L gene encodes a mitochondrial chaperone which inserts the Fe₂S₂ iron–sulfur Rieske protein into the nascent electron transfer complex III. Variants in the BCS1L gene are associated with a spectrum of mitochondrial disorders, ranging from mild to severe phenotypes. Björnstad syndrome, a milder condition, is characterized by sensorineural hearing loss (SNHL) and pili torti. More severe disorders include Complex III Deficiency, which leads to neuromuscular and metabolic dysfunctions with multi-systemic issues and Growth Retardation, Aminoaciduria, Cholestasis, Iron Overload, and Lactic Acidosis syndrome (GRACILE). The severity of these conditions varies depending on the specific BCS1L mutation and its impact on mitochondrial function. This study describes a 27-month-old child with SNHL, proximal renal tubular acidosis, woolly hypopigmented hair, developmental delay, and metabolic alterations. Genetic analysis revealed a homozygous BCS1L variant (c.38A>G, p.Asn13Ser), previously reported in a patient with a more severe phenotype that, however, was not functionally characterized. In this work, functional studies in a yeast model and patient-derived fibroblasts demonstrated that the variant impairs mitochondrial respiration, complex III activity (CIII), and also alters mitochondrial morphology in affected fibroblasts. Interestingly, we unveil a new possible mechanism of pathogenicity for BCS1L mutant protein. Since the interaction between BCS1L and CIII is increased, this suggests the formation of a BCS1L-containing nonfunctional preCIII unable to load RISP protein and complete CIII assembly. These findings support the pathogenicity of the BCS1L c.38A>G variant, suggesting altered interaction between the mutant BCS1L and CIII. Full article

Background: This study aimed to compare the clinical, pathological, and biochemical characteristics of upper rectal cancer (URC) and mid–lower rectal cancer (MLRC) in stage II and III non-metastatic rectal cancer and to identify distinct prognostic factors influencing survival and recurrence. Material and Methods: This retrospective cohort study included 100 patients with stage II and III non-metastatic rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy (nCRT) followed by curative-intent surgery between 2021 and 2024. Patients were categorized into URC (n = 53) and MLRC (n = 47) groups. Parameters analyzed included demographic factors, ASA score, surgical characteristics, pathological features (tumor stage, lymph node involvement, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, tumor regression grade (TRG)), and biochemical markers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), white blood cell (WBC) count, neutrophil count, platelet count (PLT), and C-reactive protein (CRP)). One-year overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier survival curves, and Cox regression models identified independent prognostic factors. Results: Preoperative CEA levels were higher in MLRC (p = 0.05), whereas WBC count (p = 0.01), neutrophil count (p = 0.02), PLT (p = 0.01), and CRP levels (p = 0.01) were higher in URC. Pathological analysis revealed higher LVI (p = 0.04), PNI (p = 0.04), and tumor budding (p = 0.03) in MLRC. At one-year follow-up, OS rates were 82.1% (URC) vs. 80.3% (MLRC) (p = 0.85), and DFS rates were 78.6% (URC) vs. 73.4% (MLRC) (p = 0.72). Multivariate Cox regression analysis identified age (HR: 1.04, p = 0.03), ASA score (HR: 1.22, p = 0.01), CRP (HR: 1.18, p < 0.001), preoperative CEA (HR: 1.12, p = 0.02), preoperative CA19-9 (HR: 1.09, p = 0.03), LVI (HR: 1.42, p < 0.001), PNI (HR: 1.35, p = 0.02), and tumor budding (HR: 1.28, p = 0.03) as independent prognostic factors for OS. Similar trends were observed for DFS, with T stage (HR: 1.35, p = 0.01) and tumor size (HR: 1.22, p = 0.01) also being found significant. Conclusions: Inflammatory markers, tumor burden indicators (LVI, PNI, budding, tumor size, T stage), and preoperative CEA/CA19-9 were identified as significant predictors, suggesting a risk-adapted approach to rectal cancer treatment. Full article

It has been reported that miR-375-3p plays a critical role in numerous diseases. To elucidate its biological function, particularly its differential expression and specific mechanisms of action in Alzheimer’s disease (AD) and small cell lung cancer (SCLC), this study comprehensively explores the associations between the target genes of miR-375-3p and both AD and SCLC. The focus is specifically on its impact on disease progression and the remodeling of the tumor microenvironment. We utilized databases such as the psRNATarget database and the STRING database, to construct a protein–protein interaction (PPI) network for the classification and discrimination of the miR-375-3p gene, resulting in the identification of 14 intersecting target genes. Subsequently, two key genes, ASCL1 and CHD7, along with their associated genes, were further analyzed using Spearman correlation analysis. The identified key genes were then subjected to GO function annotation and KEGG pathway enrichment analysis. It was determined that pathways related to lipid metabolism, autophagy, and cell apoptosis were differentially expressed in the AD and SCLC environments, with nine related pathways identified, among which the PI3K pathway was the most prominent. Finally, we demonstrated that the expression of miR-375-3p significantly differed between the two environments, with higher expression levels observed in AD compared to SCLC. Our study confirmed that miR-375-3p can promote apoptosis, regulate lipid metabolism, influence the progression of neurodegenerative diseases, and inhibit the proliferation and metastasis of tumor cells. These research findings may have significant implications for the future treatment of AD and SCLC. Full article

Polycyclic aromatic hydrocarbons (PAHs) and global warming impact aquatic ecosystems, eventually interacting. Monolayer (2D) cultures of cell lines, such as the rainbow trout liver RTL-W1, are employed for unveiling toxicological effects in fish. Nonetheless, three-dimensional (3D) models constitute an alternate paradigm, better emulating in vivo responses. Here, ultra-low attachment (ULA) plates were used to generate ten-day-old RTL-W1 spheroids for exposure to a control, a solvent control (0.1% DMSO) and the model PAH benzo[k]fluoranthene (BkF) at 10 and 100 nM and at 18 and 23 °C (thermal stress). After a 4-day exposure, spheroids were analyzed for viability (alamarBlue and lactate dehydrogenase), biometry (area, diameter and sphericity), histocytology (optical and electron microscopy), and mRNA levels of the detoxification-related genes cytochrome P450 (CYP)1A, CYP3A27, aryl hydrocarbon receptor (AhR), glutathione S-transferase (GST), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), multidrug resistance-associated protein 2 (MRP2) and bile salt export protein (BSEP). Immunocytochemistry (ICC) was used to assess CYP1A protein expression. Neither temperature nor BkF exposure altered the spheroids’ viability or biometry. BkF modified the cell’s ultrastructure. The expression of CYP1A was augmented with both BkF concentrations, while AhR’s increased at the higher concentration. The CYP1A protein showed a dose-dependent increase. Temperature and BkF concurrently modelled UGT’s expression, which increased in the 100 nM condition at 23 °C. Conversely, CYP3A27, MRP2, and BSEP expressions lowered at 23 °C. CAT and GST mRNA levels were uninfluenced by either stressor. Overall, BkF and temperature impacted independently or interactively in RTL-W1 spheroids. These seem to be useful novel tools for studying the liver-related effects of temperature and PAHs. Full article

Fluorinated chalcones are molecules reported to possess potent anticancer properties against triple-negative breast cancer (TNBC) cells. However, their molecular mechanisms have not yet been fully explored. Using bioinformatics tools, we analyzed the transcriptomes of MDA-MB-231 cells treated with either a novel fluorinated chalcone (compound 3) or a control in order to identify differentially expressed (DE) genes associated with its anticancer activity and determine the biological processes in which these genes are involved. A fluorinated chalcone was synthesized using the Claisen–Schmidt method. The transcriptome of MDA-MB-231 cells was then analyzed on an Illumina NextSeq500, and DE genes with significant changes in expression were identified using the DESeq2 v1.38.0 bioinformatics tool under the strict detection criteria of |log2FC| ≥  2 and adjusted p < 0.05. We identified 504 DE genes, which were enriched in terms related to “regulation of cell death”, “cation transport”, “response to topologically incorrect proteins”, and “response to unfolded proteins”. Surprisingly, these genes were involved in “the HSF1-dependent transactivation pathway” and “the attenuation phase pathway”. This bioinformatics-based study suggests that the tested fluorinated chalcone could influence HSF-1 silencing in addition to promoting the up-regulation of several genes involved in stress-induced apoptosis. Therefore, the tested compound could have enormous potential as a novel approach for TNBC treatment. Full article

Bee pollen (BP) is a very valuable bee product, and its value depends on its proteins, lipids, amino acids, carbohydrates, vitamins, minerals, and biologically active compounds such as phenolic compounds, which may change depending on the method of pollen preparation after collection and its storage conditions. Therefore, it is very important to determine when the decline in bioactive compounds in BP occurs during storage. The purpose of this study was to evaluate the changes in the content of ascorbic acid and phenolic compounds, and to determine the antioxidant activity of BP extracts depending on their preparation method and storage conditions over a 15-month period, with assessments conducted every 3 months. Dried pollen (at +28 °C on the first day and +35 °C on the second day) and frozen (−20 °C and −80 °C) BP samples were prepared. After 3 months of storage, there was no decrease of ascorbic acid in frozen BP; however, it decreased by 20% in dried BP (p < 0.05). It was determined that in frozen BP, the content of total phenolic compounds decreased by 12–14% (p < 0.05) after 6 months, and in dried BP, it decreased by 7% (p < 0.05) after 3 months. The levels of flavonoids decreased by 10–17% (p < 0.05) in BP after 6 months. Chlorogenic and p-coumaric acids have been observed as the most abundant phenolic acids in BP. During storage (the 6–15-month period), the strongest antiradical and reducing activity in vitro was estimated in the frozen (−80 °C) BP, which was 1.8–3.4-fold and 2.6–3.1-fold higher, respectively, compared to the dried BP extracts. In conclusion, significant results were obtained, showing better stability of phenolic compounds and ascorbic acid during storage in frozen BP compared to dried pollen. Melisopalynological analysis revealed a polyfloral pollen mixture, with Salix spp. and Brassica napus L. predominating in all samples, comprising 34.3% and 36.8%, respectively. Among these, Acer platanoides L., Malus domestica Borkh., and Taraxacum officinale L. were important minor pollens present in the samples examined. Full article

The purpose of this study was to investigate the effects of the optimization of dietary energy supply on the growth performance, nutrient digestibility, energy metabolism, nutrient oxidation, slaughter performance, and meat quality of growing and fattening pigs under a low-temperature environment. In this study, forty-eight 60-day-old growing barrows (Duroc × Landrace × Large White) with an initial body weight of 31.24 ± 3.56 kg were completely randomized into two treatment groups, with four replicates in each treatment group and six pigs in each replicate. The two groups were fed diets with equal protein levels and different energy levels (a conventional diet and an energy-optimized diet); the dietary energy level was increased by 8% by adding 6% fat, and the two groups were kept at the same ambient temperature (10 ± 1 °C) all day. After 5 d of prefeeding, the final weight reached approximately 110.00 kg prior to slaughter (99 days of age), and four pigs with a body weight of about 80.00 kg were selected in the two groups for digestion, metabolism, and respiratory calorimetry. The results showed that the average daily feed intake of the TES group (energy-optimized diet group, high fat and energy) was lower than that of the CON group (conventional diet group, normal fat and energy) (p < 0.05). Compared with the CON group, the feed-to-gain ratio was lower in the TES group during the fattening period (60–110 kg) (p < 0.05). Compared to the CON group, fat and energy digestibility in the TES group were higher (p < 0.05), fecal nitrogen and urine nitrogen were lower (p < 0.05), the nitrogen deposition rate increased (p < 0.05), and fat oxidation and the sedimentation energy rate also increased (p < 0.05). The serum triglyceride concentration in the TES group was higher than that in the CON group (p < 0.05). Compared to the CON group, the carcass weight, body fat content, backfat thickness, and eye muscle area in the TES group increased (p < 0.05); the L* value of flesh color also increased (p < 0.05); and the shear force was lower (p < 0.05). The dietary energy should be optimized under a low-temperature environment, and the feed conversion efficiency of fattening pigs could be improved by improving dietary energy levels by adding fat, increasing the fat oxidation proportion, promoting nitrogen deposition and sedimentation energy, and improving slaughter performance and meat quality. Full article