Search Results (635)

Macroalgae plays a significant role in the formulation of innovative and environmentally sustainable approaches to address food challenges. Specifically, green macroalgae serve as dietary supplements aimed at improving the health, growth, and feeding efficiency of various species of marine and freshwater fishes, as well as mollusks. The effects of Chaetomorpha linum extract (CLE) on growth performance, physiological responses, and disease resistance are studied in Bellamya bengalensis against Aeromonas hydrophila. In this experiment, adult B. bengalensis (4412 ± 165.25 mg) were randomly divided into 15 rectangular glass aquariums (35 snail/aquaria; 45 L capacity) and their basal diet was supplemented with different levels of CLE, including 0 (CLE0), 1 (CLE1), 2 (CLE2), 3 (CLE3), and 4 (CLE4) g/kg for 60 days. The growth performance in the CLE3 dietary group was significantly higher that of the CLE0 group, exhibiting both linear and quadratic trends in relation to dietary CLE levels (p < 0.05). The activities of pepsin, amylase, and lipase were found to be highest in CLE3 and lowest in CLE0. Both linear and quadratic responses to dietary CLE levels in digestive enzymes were observed (p < 0.05). The activities of superoxide dismutase and catalase in the hepatopancreas were found to be elevated in snails due to the synergistic effect of the supplemented CLE diet. Among different levels of diet given, CLE2-supplemented snails showed an increase in their enzyme activity (p < 0.05). Interestingly, all the CLE-treated snails expressed elevated levels of mucus lysozyme and mucus protein when compared to control (p < 0.05). Additionally, hepatopancreatic acid phosphatase and alkaline phosphatase activity were elevated in snails consuming CLE3 (p < 0.05). The transcription levels of immune-related genes, including mucin-5ac and cytochrome, were significantly elevated in snails that were fed a diet supplemented with 2–4 g of CLE/kg. Furthermore, the transcription level of the acid phosphatase-like 7 protein gene also increased in snails receiving CLE-supplemented diets. After a 14-day period of infection, snails that consumed a diet supplemented with 3–4 g/kg of CLE exhibited a notable increase in survival rates against virulent A. hydrophila. Based on the above findings, it is suggested that a diet supplemented with 3 g/kg of CLE may enhance growth, antioxidant and immune defense, and disease resistance in the freshwater snail B. bengalensis. Full article

Improving phosphorus (P) utilization in broilers is crucial for reducing feed costs and environmental pollution. Bone mineralization trait is strongly associated with P utilization in poultry and is thus often used as an alternative trait for evaluating P utilization. Dentin matrix protein 1 (DMP1), an essential matrix protein for bone mineralization and P deposition, has been shown to be actively involved in P utilization in broilers, but the underlying mechanisms remain unclear. The current study aimed to investigate the possible mechanisms whereby DMP1 regulates P utilization of poultry by using gene silencing and overexpression technologies, combined with an in vitro model of primary broiler osteoblasts. The results showed that DMP1 overexpression augmented the P utilization of broiler osteoblasts, characterized by significant increases (p < 0.001) in P utilization rate, mineralization formation, alkaline phosphatase activity, and bone gla protein content. Meanwhile, DMP1 overexpression effectively (p < 0.05) activated the focal adhesion kinase (FAK) signaling, along with obvious (p < 0.01) decreases in fibroblast growth factor 23 (FGF23) expression and production. In contrast, DMP1 silencing reversed (p < 0.05) the above effects. Consistently, FAK activation promoted (p < 0.05) P utilization accompanied by remarkable (p < 0.05) decreases in FGF23 expression and production. Furthermore, gain- and loss-of-function assays demonstrated that a high level of FGF23 contributed to impaired P utilization, while a low level was beneficial. Interestingly, blocking FAK signaling not only recovered (p < 0.05) the FGF23 expression and production in DMP1 overexpressed cells but also obviously (p < 0.05) weakened their P utilization. These findings indicate that DMP1 inhibits FGF23 expression by activating FAK, thereby contributing to P utilization in broiler osteoblasts. They reveal a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts and provide a potential target for improving P efficiency in poultry. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality among hemodialysis (HD) patients, underscoring the need for reliable biomarkers for early diagnosis and management. Serum intercellular adhesion molecule-1 (ICAM-1) has been investigated for years as a potential CVD marker but has yet to establish clinical utility. In a cohort of 142 HD patients, we examined the potential of serum ICAM-1 as a CVD biomarker and evaluated whether confounding factors, including low-grade inflammation and chronic kidney disease–mineral bone disorder (CKD-MBD), limit its diagnostic value. In addition to serum ICAM-1, routine biochemical parameters, bone alkaline phosphatase (bALP), and nitric oxide (NO) were measured. Serum levels of ICAM-1, bALP, and NO did not differ between patients with and without CVD, defined by a positive history of coronary heart disease, stroke, or peripheral arterial disease. Serum ICAM-1 concentrations were higher in HD patients with inflammation, as indicated by C-reactive protein levels >1 mg/dL. ICAM-1 showed no correlation with NO, a marker of endothelial dysfunction, but was positively correlated with bALP, a marker of CKD-MBD. In conclusion, serum ICAM-1 is not a reliable biomarker of CVD in HD patients. Its diagnostic utility appears confounded by inflammation and disturbances in bone turnover. Full article

Protein post-translational modifications (PTMs), as an important biological process of plants responding to environmental stimuli, can regulate the chemical decoration and properties of translated proteins by altering amino acid side chains or protein terminal structures, thereby affecting the synthesis, assembly, localization, function, and degradation of proteins. Notably, PTMs regulate protein function without changing protein expression levels. Two dozen types of PTMs have been identified. This review summarizes the molecular mechanisms of major types of PTMs, including phosphorylation, ubiquitination, SUMOylation, glycosylation, methylation, and acetylation, with a focus on their regulatory roles in plant responses to abiotic stresses. Under heat stress, phosphorylation activates transcription factors such as HSFA1 (heat shock transcription factor 1), while SUMOylation regulates the activity of HSFA1/HSFA2 in the heat stress signaling pathway. Upon cold stress, phosphorylation, ubiquitination, and S-acylation collectively regulate the expression of cold tolerance-related genes. The drought stress response relies on SnRK2s (Sucrose 321 non-Fermenting 1-related protein kinase 2s) -mediated phosphorylation, regulation of ARF7 (auxin response factor 7) by SUMOylation, and ubiquitination. In salt stress, the coupling of phosphorylation of SOS (salt overly sensitive) pathway-related proteins, ubiquitination, and phospholipid metabolism maintains ion homeostasis. Additionally, PTMs play a key role in ABA-mediated abiotic stress responses by regulating core components of signal transduction, such as PYR (pyrabactin resistance)/PYL (PYR1-LIKE)/RCAR (regulatory components of ABA receptor) receptors, PP2Cs (protein phosphatases type 2C), and SnRK2s. On the basis of the synthesis of the regulatory mechanisms of PTMs, we discuss how PTMs can be manipulated to breed abiotic stress resilient crops and the issues to be addressed to achieve the goal, such as crosstalk between PTMs, technical challenges in investigating PTMs and identifying PTM substrates. Full article

In this research, we sought to methodically examine the protective effects of Gastrodia elata extract (GEE) on liver damage induced by D-galactose (D-gal) in mice and clarify the underlying mechanisms. The chemical composition of GEE was characterized using Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS), while network pharmacology analysis was employed to predict potential molecular targets and signaling pathways. A mouse model of liver injury was established through daily intraperitoneal injection of D-gal over a 42-day period, during which the hepatoprotective efficacy of GEE was evaluated. Biochemical, histopathological, and molecular analyses were subsequently performed. UPLC-MS/MS identified ingredients such as amino acids, aromatic compounds, fatty acids, and terpenoids in GEE. A network pharmacology analysis enabled the identification of 272 common targets linked to GEE and liver damage, demonstrating notable enrichment within the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. In vivo experiments demonstrated that GEE effectively alleviated D-gal-induced body weight loss and elevated liver index values, alleviated hepatic histological damage, and reduced serum levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphatase (ALP). Furthermore, GEE enhanced the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), decreased malondialdehyde (MDA) levels, and downregulated the mRNA expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α). Western blot analysis confirmed that GEE activated the PI3K/Akt pathway, as evidenced by increased ratios of phosphorylated Phosphatidylinositol 3-kinase/Phosphatidylinositol 3-kinase (p-PI3K/PI3K) and phosphorylated AKT/Protein Kinase B (p-AKT/AKT); restored the B-cell lymphoma 2-associated X protein/B-cell lymphoma-2 (Bax/Bcl-2) balance; and reduced cyclin-dependent kinase inhibitor 1 (p21) expression. The results suggest that GEE protects against D-gal-induced liver damage by reducing oxidative stress, inhibiting inflammatory responses, and modulating apoptosis through the activation of the PI3K/Akt signaling pathway, providing support for its potential use in hepatoprotection. Full article

Protein phosphatase 2Cs (PP2Cs) constitute a widespread family of signaling regulators in plants and play central roles in abscisic acid (ABA)-mediated stress signaling; however, the PP2C gene family has not yet been systematically identified and characterized in pea (Pisum sativum), a salt-sensitive legume crop. In this study, we identified 89 PsPP2C genes based on domain features and sequence homology. These genes are unevenly distributed across seven chromosomes and classified into ten subfamilies, providing a comparative framework for evaluating structural and regulatory diversification within the PsPP2C family. The encoded proteins vary substantially in length, physicochemical properties, and predicted subcellular localization, while most members contain the conserved PP2Cc catalytic domain. Intra- and interspecies homology analyses identified 19 duplicated gene pairs in pea and numerous orthologous relationships with several model plants; all reliable gene pairs exhibited Ka/Ks < 1, indicating pervasive purifying selection. PsPP2C genes also showed broad variation in exon number and intron phase, and their promoter regions contained diverse light-, hormone-, and stress-related cis-elements with heterogeneous positional patterns. Expression profiling across 11 tissues revealed pronounced tissue-specific differences, with generally higher transcript abundance in roots and seeds than in other tissues. Under salt treatment, approximately 20% of PsPP2C genes displayed concentration- or time-dependent transcriptional changes. Among them, PsPP2C67 and PsPP2C82—both belonging to the clade A PP2C subfamily—exhibited the most pronounced induction under high salinity and at early stress stages. Functional annotation indicated that these two genes are involved in ABA-related processes, including regulation of abscisic acid-activated signaling pathway, plant hormone signal transduction, and MAPK signaling pathway-plant. Collectively, this study provides a systematic characterization of the PsPP2C gene family, including its structural features, evolutionary patterns, and transcriptional responses to salt stress, thereby establishing a foundation for future functional investigations. Full article

Objective: Airway hyperresponsiveness (AHR) is a hallmark feature of asthma; however, its precise molecular mechanisms remain incompletely defined. In this study, we investigated protein expression in airway smooth muscle that may contribute to AHR, using an experimental model of ovalbumin-induced allergic asthma. Methods: Guinea pigs were sensitized and challenged with ovalbumin. Airway responsiveness to histamine was assessed, and proteomic analysis of the tracheal tissue was conducted using electrophoresis followed by MALDI/TOF-TOF mass spectrometry. Specific protein bands corresponding to the myosin phosphatase target subunit 1 (MYPT1) were analyzed, and regulatory subunit of glycogen-targeted phosphatase 1 (RG1) was further evaluated through immunohistochemistry. Results: MYPT1, previously associated with AHR, was not detected in the proteomic analysis. Interestingly, an RG1 peptide was identified. Immunohistochemistry showed a differential expression pattern was observed for the RG1 and Rho-associated protein kinase 2 (ROCK2), both of which were significantly upregulated in airway smooth muscle and positively correlated with the degree of AHR. Moreover, a significant positive correlation was observed between RG1 and ROCK2 expression levels. MYPT1 and its phosphorylated forms (Thr⁶⁹⁶ and Thr⁸⁵⁰), along with ROCK1 immunostaining, did not differ from controls. Conclusions: These findings suggest that RG1, along with ROCK2, may play an important role in airway hyperresponsiveness characteristic of asthma. Full article

This review focuses on the molecular pathogenesis of Type 1 diabetes (T1D), specifically on the key autoantigens targeted by the autoimmune response and the clinical implications of their epitope specificity. T1D is characterized by the destruction of insulin-producing pancreatic β-cells. The autoimmune attack is directed against a defined set of autoantigens, primarily insulin, glutamic acid decarboxylase 65, tyrosine phosphatase-like protein, zinc transporter 8, as well as several minor autoantigens. A critical advancement in understanding the disease has been the analysis of epitope specificity, revealing that immunodominant epitopes are conformational and often localized to C-terminal protein regions, exposed during β-cell degradation. The introduction of sensitive multiplex assays for the simultaneous detection of T1D-associated autoantibodies represents a major diagnostic breakthrough. These platforms enable early diagnosis, risk stratification, and the identification of a “therapeutic window” for intervention. At this preclinical stage, antigen-specific immunotherapies aimed at restoring immune tolerance show significant promise. Ultimately, the combination of personalized diagnostic profiles, epitope mapping, and targeted therapies forms the basis for a new T1D management paradigm focused on halting the autoimmune process itself and preserving functional β-cell mass. Full article

The present study aimed to evaluate blood redox status and acute phase protein profile throughout two pharmacological treatment protocols for pyometra bitches, employing aglepristone either as a monotherapy or in combination with prostaglandin. A prospective study was conducted in 10 open-cervix pyometra bitches assigned to two groups: aglepristone (n = 5; subcutaneous injections of aglepristone on days 1, 2, and 8 after diagnosis) and aglepristone + prostaglandin (n = 5, aglepristone coupled with daily injections of cloprostenol from days 1 to 7). Blood samples were collected daily for the liver profile (alanine aminotransferase—ALT, alkaline phosphatase, and albumin), acute phase proteins (C-reactive protein-CRP, haptoglobin, and serum amyloid-A), and redox analysis [antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH), oxidative stress (TBARS), and protein oxidation]. In the aglepristone group, there was increase in albumin concentration and SOD, while protein oxidation and GSH decreased progressively throughout treatment. The aglepristone + prostaglandin group had lower ALT levels but higher lipid peroxidation, GPx, and CRP. In conclusion, the combined use of prostaglandin modified the profile of oxidative markers, antioxidant enzymes, and C-reactive protein, thereby preventing the assessment of treatment efficacy. Conversely, albumin concentration proved a sensitive marker of therapeutic effectiveness in both treatment protocols for pyometra bitches. Full article

The 26S proteasome is the main proteolytic machinery involved in protein degradation, thereby contributing to the homeostasis and stress response of eukaryotic cells. This macromolecular complex consists of a 20S core particle assembled with one or two 19S regulatory particles. Here, we describe the Plasmodium berghei (Pb) proteasome AAA-ATPase regulatory subunit Rpt3 and demonstrate its binding to the Protein Phosphatase 1 catalytic subunit (PP1c), which is one of the major and essential parasite phosphatases. The PbRpt3 protein enhances the activity of PP1c both in vitro and in a Xenopus oocyte heterologous model. Further investigation of this model suggests that the PbRpt3-PP1c interaction may occur outside of the proteasome, and it reveals that the RVxF motifs of PbRpt3 are involved in its binding and regulatory function. Moreover, the ATP-binding capacity of PbRpt3 may also contribute to its phosphatase regulatory activity. In the parasite, reverse genetic studies suggest an essential role for PbRpt3 during erythrocytic cycle of P. berghei, and an interactome analysis confirmed that PbRpt3 belongs to the 19S regulatory particle of the proteasome and may interact with proteins previously shown to be involved in phospholipid binding. Full article

The accumulation of advanced glycation end products (AGEs) is a hallmark of prolonged high glucose levels in diabetes mellitus. We have previously reported that hypoxia and AGEs cause epigenetic modification of the repressive mark H3K27me3 in podocytes by downregulation of enhancer of zeste homolog 2 (EZH2) and nuclear inhibitor of protein phosphatase 1 (NIPP1). However, their impact on proximal tubular cells remains unclear. The aim of this study was to investigate the role of AGEs and diabetes on the epigenetic modifications of EZH2 and H3K27me3 in proximal tubular cells and in diabetic (db/db) mice. Our results show that AGEs reduced EZH2 expression in TKPTS cells, thereby decreasing the tri-methylation of H3K27. qRT-PCR analysis revealed upregulation of genes known to contribute to diabetic nephropathy and kidney injury as Ctgf, Snai1, and p27^Kip1. Consistently, immunofluorescent staining of renal sections from db/db mice confirmed the reduction in H3K27me3 levels in proximal tubules compared to non-diabetic controls. In summary, we show that AGEs induce epigenetic changes in proximal tubular cells by suppressing EZH2, thereby facilitating the transcription of genes involved in progression of diabetic nephropathy. These results provide new insights into metabolic memory, a process in which prior poor glucose control triggers ongoing renal damage despite current normoglycemia. Full article

Heat stress exacerbated by global warming severely impairs the growth and tea quality of the tea plant (Camellia sinensis). Trehalose is pivotal for regulating plant growth and enhancing stress resistance. However, the molecular characteristics, expression patterns, and regulatory mechanisms of trehalose metabolism genes in tea plants under heat stress remain unclear. Therefore, this study conducted a comprehensive investigation of trehalose metabolism genes in the Tieguanyin tea plant genome. A total of 30 trehalose metabolism genes were identified, including 17 trehalose-6-phosphate synthase (CsTPS), 9 trehalose-6-phosphate phosphatase (CsTPP), and 4 trehalase (CsTRE) genes. These genes were characterized in terms of their chromosomal locations and gene structures; the encoded proteins were characterized in terms of their phylogenetic relationships, conserved motifs, functional domains, physicochemical properties, and subcellular distributions. The results showed that these genes exhibit family-specific structural and functional features, laying a foundation for further functional studies. Collinearity analysis identified 20 homologous gene pairs between tea plants and Arabidopsis thaliana, significantly more than the 3 pairs with Oryza sativa, suggesting a closer evolutionary relationship with A. thaliana. Additionally, five intraspecific duplicated gene pairs were identified, all with Ka/Ks values < 1, indicating they have undergone strong purifying selection during evolution, leading to functional stability. Cis-acting element analysis revealed abundant stress-responsive, light-responsive, and phytohormone-responsive elements in the promoter regions of these trehalose metabolism genes, indicating their potential involvement in tea plant stress resistance regulation. Differential expression analyses under heat stress with exogenous trehalose treatment (CK: control, T: water-sprayed heat stress, TT: 5.0 mM trehalose-sprayed heat stress) identified six differentially expressed genes (DEGs). We further analyzed the expression patterns of these DEGs. Specifically, CsTPS1, CsTPS5, and CsTPS12 were increasingly upregulated in CK, T, and TT, respectively, while CsTPP1 and CsTPP2 were upregulated in TT relative to T. Additionally, CsTRE1, CsTRE2, and CsTRE4 showed downregulation in TT compared to T, though they were not classified as DEGs. These findings indicate that exogenous trehalose application modulates trehalose metabolism by promoting CsTPS and CsTPP expression while inhibiting CsTRE expression, thereby increasing endogenous trehalose content in tea plants under heat stress. Yeast heat stress tolerance assays confirmed that CsTPS1, CsTPS5, CsTPS12, and CsTPP1 enhanced yeast survival at 38 °C, verifying their function in improving organismal heat stress tolerance. In conclusion, these results clarify the roles of trehalose metabolism genes in tea plants’ heat stress response, demonstrating that exogenous trehalose modulates their expression to increase endogenous trehalose levels. This study provides a theoretical foundation for exploring trehalose-mediated heat stress resistance mechanisms and improving tea plant stress tolerance via genetic engineering. Full article

Autophagy is a lysosome-mediated self-degradation process of eukaryotic cells which is critical for the elimination of cellular damage. Its capacity progressively declines with age, and this change can lead to the development of various neurodegenerative pathologies including Spinocerebellar ataxia type 1 (SCA1). SCA1 is mainly caused by mutations in the polyglutamine region of Ataxin 1 protein. In patients affected by the disease, Purkinje neurons of the cerebellum frequently undergo demise and eventually become lost. Here we tested whether two well-characterized autophagy-enhancing small molecules, AUTEN-67 and -99, which antagonize the autophagy complex Vps34 through blocking the myotubularin-related lipid phosphatase MTMR14/EDTP, have the capacity to ameliorate SCA1 symptoms. We found that in a Drosophila model of SCA1, only AUTEN-67 exerts positive effects including improvement in climbing ability and extending life span. Based on these results, we hypothesized that the two compounds influence autophagy in the brain in a neuron-specific manner. Indeed, according to data we obtained, AUTEN-67 and -99 exhibit shared and unique functional domains in the Drosophila brain. AUTENs enhance autophagy in GABAergic and dopaminergic neurons. In addition, AUTEN-67 also affect autophagy in cholinergic neurons, while AUTEN-99 trigger the process in glutaminergic neurons and motoneurons. We also observed varying efficiencies between the two AUTENs among different subtypes of cultured hippocampal neurons of mice. These data suggest that the two compounds display neuron-specific differences in exerting autophagy-enhancing effects, and may lead to a better understanding of which types of neurons autophagy could potentially be activated to treat SCA1 in human patients. Full article

Biliary tract carcinoma (BTC) is a group of highly heterogeneous malignancies arising from the biliary epithelium. Anatomically, BTC is categorized into gallbladder cancer (GBC) and cholangiocarcinoma (CCA), with the latter further subdivided into intrahepatic (iCCA), perihilar (pCCA), and distal cholangiocarcinoma (dCCA). Epidemiological studies reveal a dismal five-year survival rate of less than 20% for BTC patients, with limited responses to current chemotherapy regimens, underscoring the urgent need to unravel its complex molecular pathogenesis. Recent research has increasingly focused on the regulatory networks of post-translational modifications, particularly the ubiquitin-proteasome system (UPS), in tumorigenesis. As the largest subfamily of deubiquitinating enzymes (DUBs), ubiquitin-specific proteases (USPs) regulate the stability of key oncoproteins such as phosphatase and tensin homolog (PTEN) and c-Myc, playing pivotal roles in tumor cell proliferation, apoptosis evasion, invasion, and metastasis. This review systematically summarizes the differential expression profiles of USP family members (e.g., USP1, USP3, USP7, USP8, USP9X, USP21, and USP22) in BTC and their clinical significance, with a focus on elucidating how specific USPs regulate tumor progression through key substrates, including poly(ADP-ribose) polymerase 1 (PARP1), dynamin-1-like protein (DNM1L), and O-GlcNAc transferase (OGT). Furthermore, based on recent advances, we discuss the therapeutic potential of small-molecule USP inhibitors in BTC targeted therapy, providing a theoretical foundation for developing novel precision treatment strategies. Full article

This study characterized the biological response of MG-63 cells to synthetic, hydroxyapatite scaffolds (HAsint) fabricated via fused filament fabrication. Scaffolds were compared to 2D plate-adherent cultures using six assays: cell morphology and distribution with scanning electron microscopy and confocal laser scanning microscopy; cell proliferation and cytotoxicity via WST-1 tetrazolium assay; relative osteogenic gene expression through reverse-transcription–quantitative polymerase chain reaction, and protein synthesis via multiplex immunoassay. Data were analyzed using one-way ANOVA. Results confirmed high cell viability and uniform distribution on HAsint scaffolds. Proliferation increased significantly over 7 days, though direct cytotoxicity also increased, likely due to the static conditions of the experiment and, subsequently, the high ion reprecipitation from scaffold degradation. Importantly, HAsint scaffolds significantly enhanced osteogenic marker expression of phosphatase alkaline (ALPL), osteopontin (OPN), and osteocalcin (OCN) genes, and elevated concentrations of interleukins (IL)-6, IL-8 and matrix metalloproteinase 1 compared to plate-adherent controls. It can be concluded that 3D-printed HAsint scaffolds support robust osteogenic differentiation and proliferation despite inducing a transient cytotoxic response in vitro. The marked upregulation of key osteogenic genes and proteins confirms the scaffolds’ bioactivity and highlights their potential for bone tissue engineering applications. Full article