Search Results (11,010)

Embryogenesis is a critical process for which nutritional and metabolic signals act as informational cues that shape adipose tissue development and establish long-lasting metabolic health. Emerging evidence indicates that adipose tissue is not a passive energy storage but a developmentally and metabolically dynamic organ. Cellular composition, functional capacity, and plasticity of adipose are programmed early through coordinated transcriptional, epigenetics, and proteomics processes. Maternal environments in nutritional challenge, including overnutrition and malnutrition, influence adipocyte lineage commitment, depot-specific expansion, and metabolic functionality, predisposing offspring to divergent risks of obesity and metabolic disease. The future of perinatal adipose biology and genomics relies on integrating multi-omics approaches with an artificial intelligence (AI)-driven analytical perspective to resolve complex developmental processes and predict long-lasting metabolic health. Furthermore, the incorporation of sex-specific models is important, which will be essential for capturing biological heterogeneity and ensuring translational relevance. Together, these advance perspectives are predisposed to shift the field from descriptive associations toward predictive and preventive paradigms, reinterpreting metabolic disease risk as a modifiable consequence of early-life adipose programming rather than an inevitable outcome of later-life exposures. Full article

Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults, yet the biochemical environment within the nasolacrimal duct (NLD) remains poorly understood. This study aimed to characterize the proteomic composition of NLD lavage fluid and identify subtype-specific molecular features distinguishing membranous and mucinous obstruction. Paired tear and NLD lavage fluid (NLD-LF) samples were collected from patients undergoing dacryoendoscopic recanalization, and proteomic profiling was performed using LC–MS/MS. A total of 1345 proteins were identified in NLD-LF and 767 in tear fluid, revealing a distinct NLD-specific proteome. Although the membranous and mucinous subtypes shared broadly similar protein compositions, differentially expressed proteins highlighted divergent biochemical pathways. The membranous subtype showed enrichment of keratinization-related processes involving KRT1, KRT9, and KLK13, suggesting epithelial remodeling and cornification. In contrast, the mucinous subtype exhibited upregulation of proteins involved in lipid metabolism, carboxylic acid biosynthesis, and sulfur compound metabolism, including ALOX15B, LCAT, and GSTM4, indicating metabolic conditions that promote mucin–lipid interactions, glycan sulfation, and redox-dependent mucin cross-linking. These findings provide new insights into the protein composition of NLD lavage fluid and suggest molecular differences between the membranous and mucinous obstruction subtypes. Full article

Female reproductive aging is associated with a progressive decline in oocyte competence and reduced success in assisted reproductive technologies. While chromosomal abnormalities, mitochondrial dysfunction, and DNA damage have been extensively studied, these mechanisms do not fully explain developmental arrest in chromosomally euploid embryos or the variability in embryo competence. Human oocytes enter a transcriptionally quiescent state during meiotic maturation and rely almost entirely on the regulated translation of stored maternal messenger RNAs to support fertilization and early embryonic development until zygotic genome activation. In this context, translational fidelity becomes a critical determinant of proteome integrity and cellular function. Age-related alterations affecting ribosomal RNA integrity, transfer RNA modification, aminoacylation accuracy, and translational regulatory networks may impair the precision, timing, and coordination of protein synthesis. These defects can disrupt essential processes such as spindle assembly, cytoskeletal organization, and early cleavage dynamics, ultimately compromising embryo viability despite chromosomal normality. In addition, the follicular microenvironment, including redox balance, metabolic support, and signaling pathways, plays a crucial upstream role in maintaining translational integrity. This review integrates mechanistic evidence from molecular, cellular, and developmental studies to propose that progressive decline in translational fidelity represents a fundamental and previously underrecognized driver of reproductive aging. Understanding translational control as a central regulator of oocyte competence may provide new insights into unexplained IVF failure and support the development of novel biomarkers and therapeutic strategies aimed at preserving reproductive potential. Full article

Polyethylene (PE) is one of the most persistent pollutants in the environment. Here, we enriched a microbial consortium (PEH) and isolated a bacterial strain, Bacillus cereus PE-1, capable of degrading PE from landfill soil using PE as the sole carbon source. Scanning electron microscopy revealed significant surface erosion, while weight loss reached up to 4.57% after 30 days. TGA showed a 5.88% decrease in onset degradation temperature, and contact angle measurements indicated increased hydrophilicity. Elemental analysis confirmed oxygen incorporation into the polymer matrix. Genome sequencing revealed genes associated with biofilm formation (epsA, epsB, pgaC), oxidation (laccase, copper oxidase), hydrolysis (esterase, lipase, PHB depolymerase), and β-oxidation pathways. While these genomic findings indicate a predicted capacity for assimilation, no transcriptomic or proteomic validation was performed in this study. These findings suggest that PE-1 can colonize PE, initiate oxidative cleavage, and potentially assimilate breakdown products. This study provides new insights into the microbial degradation of polyolefins and identifies a promising bacterial candidate for plastic bioremediation. Full article

Background/Objective: GHRP-6 is a GH secretagogue hexapeptide with expanding and promising cardioprotective effects. Having determined 0.4 mg/kg as the minimum effective dose for enhancing inotropy based on echocardiographic parameters in healthy rats, we implemented a non-reperfusion myocardial infarct model, with its consequent left ventricle wall thinning and ballooning, via permanent left descending coronary artery ligation. Methods: Rats were assigned to three groups: sham-operated/normal rats, infarcted + saline-treated control rats, and infarcted + GHRP-6-administration rats. Treatments were initiated post-surgery and continued for 7 days. On day 7, the animals were echocardiographically and histologically evaluated. For mitochondrial proteomic analysis, an additional 12 healthy rats were used. Six animals received GHRP-6 or normal saline and were observed for 6 h after the inoculation. Results: Here, we show that GHRP-6 attenuated myocardial tissue demise, reduced myocardial interstitial fibrosis/scarring, and integrally improved left ventricle physiology. The proteomic analysis indicated that the GHRP-6 cardioprotective effects may be theoretically mediated by the concerted upregulation of proteins/pathways involved in fatty acid beta-oxidation, apoptosis prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Conclusions: GHRP-6 is a potent cardioprotective candidate attenuating morphological and functional outcomes caused by late ischemia. Full article

Background: Cartilage defects remain a clinical challenge due to the limited intrinsic repair capacity of hyaline cartilage, driving increasing interest in blood-derived products, including platelet-rich plasma (PRP). Variability in PRP preparation and activation protocols limits reproducibility and clinical translation, particularly in large animal models where species-specific differences are an additional cue. This study aimed to standardize and optimize in pigs a protocol for plasma rich in growth factors (PRGF), a leukocyte-poor PRP, aligned with current human clinical practice. Methods: Whole blood from six female pigs was processed via three centrifugation protocols and activated with varying CaCl₂ concentrations to evaluate gelation and morphology. PRGF was characterized through hematological analysis, ELISA-based quantification of soluble factors, and structural imaging of fibrin gel via histology and scanning electron microscopy. Data were further analyzed using protein–protein interaction networks, hierarchical clustering, and comparative human PRGF proteomic profiles. Results: Protocol with 400× g centrifugation followed by 13.3 mM CaCl₂ activation achieved the most favorable performance, yielding the highest platelet recovery, effective leukocyte clearance, and consistent formation of a well-organized fibrin network. Porcine activated PRGF showed substantial overlap in detected factors and concentration ranges with human activated PRGF prepared with the same protocol. Conclusions: These findings establish a robust, clinically aligned porcine PRGF protocol and support the pig as a relevant translational model for PRP-based regenerative strategies, providing a reliable platform for preclinical evaluation of cartilage therapies. Full article

To reduce pressure on capture fisheries, sustainable aquaculture must decrease its dependency on fish meal and fish oil. Microalgae are a promising substitute due to their complete nutritional profile and low-footprint production process. This study examined the use of the cyanobacterium Limnospira maxima (commercially known as Spirulina) as a partial substitute for fish meal in feed for juvenile Nile tilapia (Oreochromis niloticus). We developed isoproteic (36%) and isoenergetic (3000 kcal kg⁻¹) fish feed formulations containing 0% (control), 10%, 20%, 30%, or 40% L. maxima dry biomass. The experimental diets were then fed to 360 juvenile O. niloticus (1.32 ± 0.35 g) for 85 days using a randomized experimental design. The hepatic, intestinal, and muscle (fillet) tissues of the fish were collected for morphophysiological, fatty acid, and proteomic analyses. The intestinal coefficient, number of intestinal villi, villus height, and hepatosomatic index were essentially the same for all treatments (p > 0.05). Treatments containing 20–30% L. maxima exhibited a higher degree of unsaturation and better dietary fat quality. A greater abundance of the enzymes SOD, GSR, PRX1, and PLD3 in the experimental groups indicated higher antioxidant activity, whereas a greater abundance of acyl-CoA dehydrogenases indicated better use of fatty acids as an energy source. These trends were more evident in the 20–30% inclusion range. Thus, adding L. maxima to fish feed improves farming performance, fish health, and product quality. The results encourage the use of microalgae to promote more sustainable aquaculture. Full article

Immune thrombocytopenia (ITP) is a hematological disorder commonly found in individuals of any gender, race, or age. Patients with ITP will present with thrombocytopenia either in a primary form or because of an infection or a dysfunction in the immune system. The severity of ITP is linked to diminished production of platelets due to the blockage of production in the bone marrow niche and increased destruction of platelets, which confirms the diagnosis of the disorder. The investigation of the pathogenesis of ITP is of critical importance as it can give an important indication of the state of the patient, guiding us through risk assessment and treatment. Proteomics can provide tools to explore the protein profile of ITP. In this review, we aimed to uncover different biomarkers, both diagnostic and prognostic, that have been investigated with proteomic methodologies and that might help in understanding the pathogenesis of ITP and providing personalized treatment to patients. Several differentially abundant proteins were identified, including haptoglobin isoforms, heat shock proteins (HSPA6, HSPA8), integrin β3 (ITGB3), 14-3-3 protein eta (YWHAH), vitamin D-binding protein, fibrinogen chains, MYH9, and FETUB, which are involved in key signaling pathways, such as PI3K/akt, TNF-a, and mTOR, and they demonstrate potential as diagnostic and prognostic biomarkers. Collectively, current data support the value of proteomics for uncovering the molecular landscape of ITP and guiding the development of precision diagnostics and personalized therapeutic strategies. Full article

Receptor protein tyrosine phosphatases (RPTPs) are transmembrane enzymes that counterbalance protein tyrosine kinase activity by catalyzing the removal of phosphate groups from tyrosine residues on target proteins. Despite their critical roles in regulating cellular proliferation, adhesion, differentiation, and survival, RPTPs remain significantly understudied compared to their kinase counterparts. Contrary to early assumptions that PTPs function as constitutive housekeeping enzymes, emerging evidence demonstrates that RPTPs exhibit highly context-dependent roles in cancer, functioning as tumor suppressors or tumor promoters, or displaying dual activities depending on tissue type, cellular environment, and the specific signaling networks involved. This review provides a comprehensive analysis of RPTP structure, catalytic mechanisms, regulatory processes, and interactions with signaling effectors in cancer. Through a systematic examination of RPTP expression patterns across ten cancer types using Clinical Proteomic Tumor Analysis Consortium (CPTAC) and International Cancer Proteogenome Consortium (ICPC) datasets, we identify subfamily-specific and cancer-type-specific expression alterations that correlate with established functional classifications. PTPσ and PTPμ emerge as uniformly downregulated tumor suppressors across diverse malignancies, whereas PTPα and PTPε display oncogenic potential by activating Src family kinases. Context-dependent RPTPs, such as LAR and DEP-1, exhibit variable expression patterns that reflect their complex, multifaceted signaling roles. These findings establish RPTPs as critical regulators of cancer signaling with significant therapeutic potential while underscoring the need to understand tissue-specific signaling architectures when developing RPTP-targeted interventions. Full article

Background: Endometriosis is a major cause of female infertility. It significantly impacts oocyte quality and embryonic development. The condition’s pathophysiological mechanisms are multifactorial. However, they are believed to be reflected in the biochemical composition of follicular fluid (FF). FF is the immediate microenvironment of the developing oocyte hence its relevance. Conventional analytical methods provide only a limited view of this complex biofluid. This underlies the need for holistic profiling techniques. Objective: This narrative review synthesizes current knowledge on the potential of Fourier-Transform Infrared (FTIR) and Raman spectroscopy. The two are scrutinized as label-free, non-destructive tools for analyzing FF in the context of endometriosis. As such, the aim is to bridge the understanding of the disease’s impact on the follicular niche with the analytical power of these spectroscopic techniques, ultimately highlighting a critical research gap, while critically evaluating the translational pathway required to bring these techniques from research laboratories into routine clinical IVF practice. This includes assessment of practical feasibility, cost-effectiveness, turnaround time, standardization requirements, and comparison with existing clinical biomarkers. Methods: We outline the fundamental principles of FTIR and Raman spectroscopy and their complementary strengths. The review then consolidates evidence from proteomic and metabolomic studies demonstrating FF alterations in endometriosis. We also showcase the successful application of vibrational spectroscopy in other reproductive diagnostics. This synthesis is vital to identifying a specific unmet need in the field. Conclusions: Despite the known importance of FF and the proven capability of FTIR and Raman spectroscopy in related areas, there is a striking lack of studies applying these techniques directly to the FF of women with endometriosis. This review concludes by framing this void as a pivotal research opportunity. In doing so, it presents a direct rationale and methodological framework for a future study designed to characterize the unique spectral fingerprints of endometriosis in FF, with the goal of uncovering novel biomarkers and pathophysiological insights. Full article

Diapause enables insect survival in unfavorable environments. The parasitic wasp A. japonicus, a natural enemy of several fruit-tree pests, undergoes larval diapause. Previous work has shown that larval diapause in A. japonicus can be induced by medium temperatures in combination with short-day photoperiods; however, the molecular functions associated with this response remain poorly understood. Here, integrated transcriptomic and proteomic approaches were employed to investigate the molecular signatures associated with larval diapause in A. japonicus. The identification of 3399 differentially expressed genes and 3112 differentially expressed proteins was carried out between diapause and non-diapause larvae. Among these, five gene–protein pairs showed consistent differential expression, including farnesol dehydrogenase, crystallin (associated with longevity-related pathways), forkhead-associated (FHA) domain-containing proteins, and the detoxification enzyme cytochrome P450. These findings show that larval diapause in A. japonicus is accompanied by extensive physiological and biochemical remodeling, and juvenile hormone-related signaling is likely involved in this process. In summary, these results provide insights into future gene function research, especially with regard to the mechanism of larval diapause in A. japonicus. Full article

Accurate prediction of submitochondrial localization is fundamental to understanding mitochondrial biogenesis and cellular metabolic pathways. While deep representations from pre-trained protein language models (pLMs) have significantly advanced the field, traditional global average pooling methods often fail to capture critical, localized N-terminal targeting signals, particularly in long sequences where these motifs are mathematically diluted. To resolve this “signal dilution” bottleneck, we developed a multi-scale architecture that explicitly integrates high-resolution N-terminal features with global evolutionary context derived from ESM-2 embeddings. The proposed framework utilizes an orthogonal mixing strategy consisting of Token-mixing and Channel-mixing. Token-mixing is specifically designed to detect spatial rhythmic patterns across residue positions, while Channel-mixing refines the biochemical signatures within the latent feature space. Extensive benchmarking across diverse datasets demonstrates that our approach effectively maintains signal integrity. Compared to existing state-of-the-art methods, the model achieves a superior overall Generalized Correlation Coefficient (GCC) of 0.7443 on the SM424-18 dataset and 0.7878 on the SubMitoPred dataset, outperforming the latest benchmarks by 9.4% and 16.1%, respectively. Furthermore, on the independent M983 test set, our method maintained a high GCC of 0.6945, demonstrating a 9.9% improvement relative to the state-of-the-art methods. This robust and efficient framework provides a high-precision tool for large-scale mitochondrial proteomics. Full article

Mushrooms offer a promising solution for sustainable food production due to their nutritional value, low resource requirements, and ability to grow in diverse environments. As interest in mushrooms grows, it is important to understand where current research is focused and where key gaps remain. A bibliometric analysis of 776 research articles indexed in Web of Science revealed a strong emphasis on yield, substrate reuse, and enzymatic degradation, but limited attention to molecular approaches, climate adaptation, and studies from arid regions such as the Middle East. Building on these findings, this review explores the ecological diversity of mushrooms and their adaptations across tropical, temperate, boreal, and arid ecosystems. It discusses the role of mycorrhizal and microbial interactions in nutrient cycling and environmental resilience, including desert truffle symbioses. Key pathways and genetic regulation involved in lignin degradation are outlined, along with recent advancements in transcriptomics, proteomics, genomics, metabolomics, and metagenomics that support improved cultivation and bioactive compound production. The review also addresses sustainable practices, such as microbiome integration and resource recycling, to enhance mushroom farming. The aim is to bring together ecological insights and molecular strategies to support sustainable mushroom production, particularly in regions facing resource and climate challenges. Full article

Altered extracellular matrix (ECM), a hallmark of solid tumors, affects cellular survival, migration and differentiation. Typically viewed as tumor-suppressive, evidence suggests that apoptosis can also generate pro-tumoral signals. We previously showed that ECM from high-grade astrocytomas induces extensive endothelial anoikis, while a surviving subpopulation fails to form tubular structures (tubulogenesis-defective endothelial cells, or TDECs). We combined functional assays with whole-cell proteomics to investigate this response. Using real-time video microscopy, we found that apoptotic endothelial cells induced by tumor ECM attracted migrating endothelial cells and guided sprouting. Conditioned media from apoptotic endothelial cells contained a 2.8-fold increase in extracellular vesicles (EVs) relative to autologous ECM-primed endothelial cells. Although both EV populations improved TDEC tubulogenesis, only EVs produced upon tumor-ECM stimulation induced TDEC migration—a property lost when using EVs secreted by endothelial cells growing on TN-C-depleted matrices. Proteomic profiling revealed that TDECs shift from an adhesion-anchored to a microtubule-rich and glycolytically rewired phenotype, with upregulation of vesicle-trafficking regulators (ARF1/3/4, ANXA2/5), migration drivers (RAC1/3, RHOA/C, WDR1, FSCN1) and glycolytic enzymes (ENO1, ALDOA, PKM, LDHA), alongside the suppression of integrin- and cytoskeletal-anchoring proteins. Collectively, these findings indicate that tumor-ECM-driven endothelial apoptosis generates reversible reprogramming and an EV-mediated autocrine mechanism that may favor angiogenic balance. Full article

Background/Objectives: Eupalinolide B (EB), a natural compound derived from Eupatorium lindleyanum DC, has demonstrated multiple pharmacological activities. However, its role in modulating oxidative stress remains incompletely understood. Methods: In this study, we investigated the antioxidant effect and underlying mechanism of EB in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results: EB significantly attenuated LPS-induced oxidative stress as evidenced by reduced levels of intracellular reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) alongside enhanced superoxide dismutase (SOD) activity and an increased reduced/oxidized glutathione (GSH/GSSG) ratio. Using activity-based protein profiling, we identified peroxiredoxin 4 (PRDX4) as a key binding target of EB. Direct interaction was confirmed through labeling and competitive binding assays with purified PRDX4 protein. High-resolution mass spectrometry revealed that EB covalently binds to Cys54 and Cys248 residues of PRDX4. Furthermore, EB treatment upregulated PRDX4 protein expression in LPS-stimulated RAW264.7 cells. siRNA-mediated knockdown of PRDX4 significantly blunted the antioxidant effects of EB, confirming the functional relevance of this target. Conclusions: Our findings demonstrate that EB alleviates LPS-induced oxidative stress in macrophages by covalently binding to and stabilizing PRDX4, thereby enhancing cellular antioxidant capacity. This study unveils a novel mechanism whereby a natural product enhances cellular antioxidant capacity by covalently stabilizing a key peroxidase, highlighting the potential of EB as a therapeutic agent and PRDX4 as a promising target for oxidative stress-related diseases. Full article