Search Results (246)

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Listeria monocytogenes poses health threats due to its resilience and potential to cause severe infections, especially in vulnerable populations. Plant extracts and/or phytocomplexes have demonstrated the capability of natural compounds in mitigating L. monocytogenes virulence. Here we explored the suitability of a computational pipeline envisioned to identify the molecular determinants for the recognition between the bacterial protein internalin A (InlA) and the human E-cadherin (Ecad), which is the first step leading to internalization. This pipeline consists of molecular docking and extended atomistic molecular dynamics simulations to identify key interaction clusters between InlA and Ecad. It exploits this information in the screening of chemical libraries of natural compounds that might competitively interact with InIA and hence impede the formation of the InIA–Ecad complex. This strategy was effective in providing a molecular model for the anti-adhesive activity of punicalagin and disclosed two natural phenolic compounds with a similar interaction pattern. Besides elucidating key aspects of the mutual recognition between InIA and Ecad, this study provides a molecular basis about the mechanistic underpinnings of the anti-adhesive action of punicalagin that enable application against L. monocytogenes. Full article

A single domain antibody (SDAb) targeting canine PD-1 was developed as a potential immunotherapeutic for canine cancer. An alpaca was immunized with canine PD-1 protein, and a phage-display library was constructed using mRNA isolated from peripheral lymphocytes. Screening of the library yielded multiple SDAb candidates capable of nanomolar binding to canine PD-1. Among these, clone STX-1b5 demonstrated high expression in a yeast-based recombinant system and was selected for further characterization. Binding and competition assays using ELISA confirmed its ability to bind canine PD-1 and block PDL-1 interaction. In silico structural modeling supported the interaction of STX-1b5 with key PD-1 residues implicated in ligand binding. These findings support the feasibility of using SDAbs and cost-effective yeast expression systems to generate immunotherapeutics for veterinary use, with STX-1b5 representing a promising lead candidate for future clinical development. Full article

As consumer demand for quality fish products continues to rise, quality has become a key factor in market competition. Ecological aquaculture research is exploring various farming methods to balance high-quality demand with environmental protection. This study compared three aquaculture models—cage culture (CG), recirculating aquaculture (RAG), and rice–fish co-culture (RG)—by analyzing muscle quality (AOAC, GC-MS), intestinal microbiota (16S rRNA), and liver metabolism (LC-MS) to assess their effects on M. albus. In terms of muscle quality, the RG group showed increased levels of EPA and DHA, reduced muscle moisture and crude lipid content, and enhanced crude protein accumulation. The crude protein content was significantly higher in the RAG group than in the CG group (p < 0.05). The RG group also had the highest levels of total, essential, and umami amino acids, followed by the RAG and CG groups. In terms of intestinal microbiota, the RG group had the highest microbial diversity and stability, with increased abundance of Firmicutes and Bacteroidetes and decreased levels of Proteobacteria. Compared to the CG, the RAG group also showed increased microbial diversity and a reduction in pathogenic genera. Liver metabolomics analysis demonstrated that the RG group had significant advantages over the CG group in amino acid, lipid, and energy metabolism. The RAG group exhibited upregulation of glycerophospholipid metabolism and a decrease in oxidative stress marker levels. Overall, the RG group enhanced muscle quality and optimized intestinal and liver metabolism in M. albus. Full article

Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the expression of the NPM-ALK fusion oncogene. Most previous preclinical models of ALK+ ALCL were based on overexpression of the NPM-ALK cDNA from heterologous promoters. Due to the enforced expression, this approach is prone to artifacts arising from synthetic overexpression, promoter competition and insertional variation. Methods: To improve the existing ALCL models and more closely recapitulate the oncogenic events in ALK+ ALCL, we employed CRISPR/Cas-based chromosomal engineering to selectively introduce translocations between the Npm1 and Alk gene loci in murine cells. Results: By inducing precise DNA cleavage at the syntenic loci on chromosome 11 and 17 in a murine IL-3-dependent Ba/F3 reporter cell line, we generated de novo Npm-Alk translocations in vivo, leading to IL-3-independent cell growth. To verify efficient recombination, we analyzed the expression of the NPM-ALK fusion protein in the recombined cells and could also show the t(11;17) in the IL-3 independent Ba/F3 cells. Subsequent functional testing of these cells using an Alk-inhibitor showed exquisite responsiveness towards Crizotinib, demonstrating strong dependence on the newly generated ALK fusion oncoprotein. Furthermore, a comparison of the gene expression pattern between Ba/F3 cells overexpressing the Npm-Alk cDNA with Ba/F3 cells transformed by CRISPR-mediated Npm-Alk translocation indicated that, while broadly overlapping, a set of pathways including the unfolded protein response pathway was increased in the Npm-Alk overexpression model, suggesting increased reactive changes induced by exogenous overexpression of Npm-Alk. Furthermore, we observed clustered expression changes in genes located in chromosomal regions close to the breakpoint in the new CRISPR-based model, indicating positional effects on gene expression mediated by the translocation event, which are not part of the older models. Conclusions: Thus, CRISPR-mediated recombination provides a novel and more faithful approach to model oncogenic translocations, which may lead to an improved understanding of the molecular pathogenesis of ALCL and enable more accurate therapeutic models of malignancies driven by oncogenic fusion proteins. Full article

Background: The COVID-19 (coronavirus disease 19) pandemic has underscored the urgent need for effective antiviral agents targeting viral entry mechanisms. This study investigated the inhibitory effects of heparan sulfate (HS) and enoxaparin (EX) on the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor. Methods: A pseudovirus model was employed to evaluate the efficacy of HS and EX under different treatment strategies: pre-treatment of host cells, pre-treatment of the viral particles, and simultaneous co-treatment. Results: Both compounds significantly inhibited viral entry. EX exhibited a dose-dependent effect under all treatment conditions. In cell pre-treatment, EX achieved the highest levels of inhibition, whereas HS demonstrated consistent inhibitory activity that was largely concentration-independent. Viral pre-treatment revealed that both compounds effectively reduced infectivity by interfering directly with viral particles. In the co-treatment experiments, HS demonstrated superior inhibitory activity at lower concentrations compared to EX. Conclusions: The results suggested that HS and EX inhibit SARS-CoV-2 entry via distinct mechanisms. HS likely acts via competitive inhibition at the host cell surface, while EX may bind directly to the spike protein, thereby preventing engagement with the ACE2 receptor. These findings highlight the therapeutic potential of HS and EX as entry inhibitors targeting the early stages of SARS-CoV-2 infection. Further studies are warranted to evaluate their efficacy against emerging variants and in vivo models. Full article

This study addresses the urgent need for the rapid, non-destructive assessment of key soybean components, including moisture, fat, and protein, using near-infrared (NIR) spectroscopy. This study provides technical and theoretical support for achieving the efficient and accurate detection of major soybean components and for the development of portable near-infrared (NIR) instruments. Thirty soybean samples from diverse sources were collected, and 360 spectral measurements were acquired using a 900–1700 nm NIR spectrometer after grinding and standardized sampling. To improve model robustness, preprocessing strategies such as standard normal variate (SNV), multiplicative scatter correction (MSC), and Savitzky–Golay derivatives were applied. Feature selection was conducted using competitive adaptive reweighted sampling (CARS), successive projections algorithm (SPA), and uninformative variable elimination (UVE), followed by model construction with partial least squares regression (PLSR), support vector regression (SVR), and random forest (RF). Comparative analysis revealed that the RF model consistently outperformed the others across most combinations. Specifically, the SPASNV + D₁–RF combination achieved an RPD of 14.7 for moisture, CARS–SNV + D₁–RF reached 5.9 for protein, and CARS–SG + D₂–RF attained 12.0 for fat, all significantly surpassing alternative methods and demonstrating a strong nonlinear learning capacity and predictive precision. These findings show that integrating optimal preprocessing and feature selection strategies can markedly enhance the predictive accuracy in NIR-based soybean analyses. The RF model offers exceptional stability and performance, providing both technical reference and theoretical support for the development of portable NIR devices and practical rapid-quality assessment systems for soybeans in industrial applications. Full article

Background/Objectives: Hepatic steatosis, characterized by abnormal fat accumulation in the liver, is a major health concern with limited effective treatments. Goat milk whey proteins have demonstrated various therapeutic benefits. This study aimed to evaluate the hepatoprotective effects of goat whey protein hydrolysate (GWPH) on high-fructose corn syrup (HFCS)-induced hepatic steatosis in a murine model. Methods: The GWPH was prepared through enzymatic hydrolysis using Alcalase^® and divided into fractions: GWPH03 (<3 kDa), GWPH0310 (3–10 kDa), GWPH1030 (10–30 kDa), and GWPH30 (>30 kDa). These fractions were administered to respective GWPH treatment groups at 200 mg/kg b.w/day via intragastric gavage for 8 weeks, with HFCS provided to all groups except the Naïve group. After dietary intervention, an oral glucose tolerance test (OGTT) was performed, and the mice were then sacrificed for further analysis. Results: Our results demonstrate that GWPH mitigates HFCS-induced hepatic steatosis, reduces body weight gain, improves glucose homeostasis, alleviates liver injury, and regulates hepatic lipid metabolism. Notably, GWPH treatment significantly suppressed hepatic fatty acid synthase (FASN) expressions, indicating reduced de novo lipogenesis (DNL). Molecular docking of the identified peptides from GWPH—particularly PFNVYNVV, which showed strong binding affinity for KHK—suggests that it has potential as a competitive inhibitor of fructose metabolism. Conclusions: Collectively, our findings suggest that GWPH and its derived peptides could be promising candidates for managing hepatic steatosis and related metabolic abnormalities. Full article

The production of duckweed (Lemnaceae) as a novel protein source could make a valuable contribution to human nutrition. The greatly reduced habitus of duckweed enables simple cultivation with extremely low space requirements, making this free-floating freshwater plant ideal for substrate-free and vertical cultivation in controlled environment agriculture. Of particular importance in the design of a plant-producing Indoor Vertical Farming process is the determination of light intensity, as artificial lighting is generally the most energy-intensive feature of daylight-independent cultivation systems. In order to make the production process both cost-effective and low emission in the future, it is, therefore, crucial to understand and mathematically describe the primary metabolism, in particular the light utilization efficiency. To achieve this, a growth model was developed that mathematically describes the combined effects of plant density and light intensity on the growth rate of Lemna minor L. and physiologically explains the intraspecific competition of plants for light through mutual shading. Furthermore, the growth model can be utilized to derive environmental and process parameters, including optimum harvest quantities and efficiency-optimized light intensities to improve the production process. Full article

Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and inflammatory dermatoses. CK2 overactivation fosters keratinocyte proliferation and pro-inflammatory cytokine production through the STAT3 and Akt pathways in psoriasis, thus contributing to epidermal hyperplasia and inflammation. In the realm of oncology, CK2 overexpression correlates with tumor progression, facilitating cell survival and metastasis in melanoma and non-melanoma skin cancers. Pharmacological inhibition of CK2 has demonstrated therapeutic potential, with CX-4945 (Silmitasertib) as the most studied adenosine triphosphate-competitive inhibitor (ATP-competitive inhibitor). Preclinical models reveal that CK2 inhibitors effectively mitigate pathological features of psoriasis, regulate keratinocyte differentiation, and suppress tumor growth in skin cancers. These inhibitors also potentiate the efficacy of conventional chemotherapeutics and exhibit anti-inflammatory effects in dermatological conditions. Future research will aim to enhance the specificity and delivery of CK2-targeting therapies, including topical formulations, to minimize systemic side effects. Combination therapies integrating CK2 inhibitors with other agents might offer synergistic benefits in managing skin diseases. This review underscores CK2’s critical role in skin and its therapeutic potential as a pharmacological target, advocating for innovative approaches to harness CK2 inhibition in dermatology. Full article

Background: Adverse cardiac remodeling drives heart failure progression, but the role of hyaluronan-binding protein (HYBID) in this process remains unclear. This study investigated the role of HYBID as a key profibrotic factor in the progression of adverse cardiac remodeling with a focus on its functional impact on cardiac fibroblasts and underlying molecular mechanisms. Methods: RNA sequencing analysis was employed to identify differentially expressed genes in mouse ventricular tissue post-myocardial infarction (MI). Fibroblast-specific genetically modified mouse models (knockdown and overexpression) were generated using FSP1 promoter-driven adeno-associated viruses. Comprehensive histological and biochemical assessments were conducted both in vivo and in vitro to evaluate the effects of HYBID modulation on cardiac remodeling. Molecular docking and immunoprecipitation assays were utilized to elucidate the mechanistic interactions between HYBID and its downstream targets. Results: RNA sequencing revealed HYBID as a fibroblast-enriched protein significantly upregulated in myocardial tissue of MI mice. Fibroblast-specific knockdown of HYBID attenuated MI-induced fibroblast activation, improved cardiac function, and mitigated adverse cardiac remodeling. Conversely, HYBID overexpression exacerbated fibroblast activation and promoted cardiac remodeling. Mechanistically, HYBID was found to competitively bind to STAT5A, thereby inhibiting the anti-fibrotic effects of MMP13 and driving fibroblast activation and adverse remodeling post-MI. Conclusions: Our findings establish HYBID as a novel fibroblast-enriched regulator that exacerbates fibrosis and adverse cardiac remodeling following MI. By uncovering the HYBID–STAT5A–MMP13 axis as a critical signaling pathway, this study provides new insights into the molecular mechanisms underlying heart failure progression. Full article

Surimi gel, a type of hydrocolloidal food, is formed through the gelation of fish meat proteins. Myosin heavy chain (MHC), a key myofibrillar protein, plays a crucial role in the formation of the gel network via both transglutaminase (TGase)-catalyzed and non-enzymatic polymerization. Gel disintegration in surimi is primarily attributed to the proteolytic degradation of MHC. This study focused on golden threadfin bream Nemipterus virgatus, a species characterized by low TGase activity and high protease activity at elevated temperatures. We investigated the competition between non-enzymatic polymerization and proteolytic degradation of MHC and their effects on gel mechanical properties using a mathematical model. A mathematical model based on kinetic reactions accurately reflected the changes in MHC observed through SDS-PAGE analysis during N. virgatus gel disintegration. Our results indicate that not only unpolymerized but also polymerized MHC was significantly degraded, which substantially contributed to the reduction in the mechanical properties of the N. virgatus surimi. Mathematically understanding the dynamics of MHC in surimi during heating helps promote the utilization of noncommercial fish species for surimi processing by enabling better control over surimi gel properties. Full article

Sialyllactose (SL), a bioactive trisaccharide abundant in porcine colostrum, demonstrates multifunctional properties including antimicrobial activity, immune regulation, and apoptosis inhibition. This research uncovers the mechanisms by which SL mitigates enterotoxigenic Escherichia coli (ETEC)-mediated damage to intestinal barrier integrity, employing IPEC-J2 porcine epithelial models. SL pre-treatment effectively blocked pathogen adhesion by competitively binding to cellular receptors, concurrently mitigating inflammation through significant suppression of TNF-α, IL-1β, and IL-6 expression (p < 0.05). Notably, SL exhibited functional parallels to the NF-κB inhibitor BAY11-7082, jointly enhancing tight junction integrity via ZO-1 protein stabilization and inhibiting pro-inflammatory signaling through coordinated suppression of IκB-α/NF-κB phosphorylation cascades. The dual-action mechanism combines molecular interception of microbial attachment with intracellular modulation of the TLR4/MyD88/NF-κB pathway, effectively resolving both pathogenic colonization and inflammatory amplification. These findings position SL as a potential therapeutic application nutraceutical for livestock, with the capacity to address post-weaning porcine enteritis through functional feed formulations that synergistically enhance intestinal barrier resilience while curbing ETEC-mediated inflammatory pathogenesis. Full article

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, a potentially devastating disease to fetuses and immunocompromised individuals. Among its microneme proteins, MIC1 and MIC4 play crucial roles in host-parasite interactions, facilitating adhesion by binding glycans on host cells. Beyond these roles, these lectins have been implicated in modulating immune responses and inducing apoptosis, but their effects on human immune cells remain unclear. Here, we investigated the interaction of recombinant MIC1 (rMIC1) and rMIC4 with Jurkat T lymphocytes, a human immune cell model. Both lectins bound Jurkat cells in a carbohydrate-dependent manner, with rMIC4 showing competitive binding over rMIC1. Importantly, we observed that rMIC1 and rMIC4 reduced Jurkat cell viability in a time- and dose-dependent manner, inducing apoptosis through caspase activation by extrinsic and intrinsic pathways. The apoptosis was driven by reactive oxygen species production via the NADPH oxidase complex and the activation of p38 and JNK MAPK signaling pathways, emphasizing the ability of these lectins to modulate cellular signaling cascades. This study offers insights into the mechanisms involved in MIC1 and MIC4 interactions with immune cells. Full article

Objectives: Taekwondo performance is influenced by a complex and dynamic interplay of physical, nutritional, and psychological factors, all of which contribute to competitive success. However, the gender-specific relationships among these factors in young high-performance athletes remain understudied. This study aimed to fill in this knowledge gap. Methods: A cross-sectional study was conducted with 35 elite taekwondo athletes (male: n = 20, female: n = 15, age: 13 ± 1 years). Participants underwent anthropometric assessments, dietary evaluations, and psychological skill assessments during an 8-week training camp before the World Taekwondo Championships. Physical performance was assessed using the Frequency Speed of Kick Test (FSKT_mult) and the Taekwondo-Specific Agility Test (TSAT). Statistical analyses included independent t-tests, correlation analyses, and regression models. Results: Males exhibited significantly higher fat-free mass (FFM: 42.8 ± 2.9 kg vs. 36.3 ± 1.6 kg, p < 0.001), skeletal muscle mass (SMM: 31.1 ± 2.2 kg vs. 28.2 ± 1.6 kg, p < 0.001), and energy intake (32.4 ± 4.6 kcal/kg vs. 29.3 ± 3.1 kcal/kg, p = 0.032) than females. Males also had greater dietary intakes of vitamin A, vitamin C, magnesium, and iron (all p < 0.05). There were no gender differences in any psychological attributes associated with emotional intelligence, sport success perception, and mental toughness. Although the total kick count in the FSKT_mult was similar for male and female taekwondo athletes (100.2 ± 4.6 vs. 97.5 ± 5.9 kicks, p = 0.139), males outperformed females in round 4 (19.4 ± 1.1 vs. 18.6 ± 1.4 kicks, p = 0.048) and round 5 (18.2 ± 1.0 vs. 17.2 ± 1.0 kicks, p = 0.007) of this test, suggesting higher physical performance maintenance during the test. Regression models indicated that body mass (β = 0.901, p < 0.001) and calcium intake (β = 0.284, p = 0.011) predicted performance in males, while body mass (β = 1.372, p < 0.001), protein intake (β = 0.171, p = 0.012), and emotional regulation (β = 0.174, p = 0.012) were key predictors in females. Conclusions: These findings highlight the importance of an integrated approach to training, nutrition, and psychological preparation in optimizing taekwondo performance. While males and females demonstrated similar psychological resilience and total kick output in a taekwondo-specific test, males exhibited superior endurance in later test rounds of this test. Performance optimization in young elite taekwondo athletes may require the implementation of gender-specific training and nutrition strategies, emphasizing body weight control and calcium intake for males and protein intake for females. Full article