Search Results (2,658)

Recent advances in microbial bioremediation have significantly enhanced the effectiveness of wastewater management, offering innovative and sustainable alternatives to conventional treatment methods. Microorganisms, including bacteria, fungi, and algae, are increasingly recognized for their remarkable ability to degrade, transform, and remove a broad spectrum of pollutants such as organic compounds, heavy metals, and emerging contaminants from wastewater. Cutting-edge research has led to the development of novel approaches such as bioaugmentation, bio-stimulation, and the use of genetically engineered microbes, which have improved the efficiency, specificity, and resilience of bioremediation processes. The application of microbial consortia and advanced bioreactor designs further optimizes pollutant removal under diverse environmental conditions. Additionally, omics technologies and systems biology are providing deeper insights into microbial community dynamics and metabolic pathways, enabling the fine-tuning of bioremediation strategies for targeted outcomes. Despite ongoing challenges related to scalability, environmental variability, and regulatory considerations, these advances are paving the way for more robust, cost-effective, and eco-friendly wastewater management solutions. Overall, the integration of innovative microbial technologies holds great promise for addressing global water quality challenges and promoting environmental sustainability. Full article

Alzheimer’s disease is driven by multiple molecular drivers, including the pathological behavior of two intrinsically disordered proteins, amyloid-β (Aβ) and tau, whose aggregation is regulated by sequence-encoded ensembles and liquid–liquid phase separation (LLPS). This review integrates recent advances in biophysics, structural biology, and computational modeling to provide a multiscale perspective on how sequence determinants, post-translational modifications, and protein dynamics regulate the conformational landscapes of Aβ and tau. We discuss sequence-to-ensemble principles, from charge patterning and aromatic binders to familial mutations that reprogram structural ensembles and modulate LLPS. Structural studies, including NMR, SAXS, cryo-EM, and cryo-electron tomography, trace transitions from disordered monomers to fibrils and tissue-level structures. We highlight experimental challenges in LLPS assays, emerging standards for reproducibility, e.g., LLPSDB, PhaSePro, and FUS benchmarks, and computational strategies to refine and condensate modeling. Finally, we explore the therapeutic implications, including condensate-aware medicinal chemistry, ensemble-driven docking, and novel insights from clinical trials of anti-Aβ antibodies. Together, these perspectives underscore a paradigm shift toward environment- and ensemble-aware therapeutic design for Alzheimer’s and related protein condensation disorders. Full article

A central challenge in functional genomics is understanding the difference between correlative transcriptomic observations and definitive causal understanding of gene function in vivo. Poultry skeletal muscle, a system of significant agricultural and biological importance, demonstrates this challenge. While transcriptomic studies have cataloged extensive RNA expression dynamics during muscle development and in growth-related myopathies like wooden breast, establishing causative roles for these molecules is lacking. This review synthesizes how advanced genetic tools are now enabling a shift from correlation to causation in avian muscle biology. We detail how viral vectors (e.g., adenovirus, lentivirus, and RCAS) and CRISPR/Cas9 systems have provided direct in vivo validation of the functional roles of specific mRNAs, miRNAs, lncRNAs, and circRNAs in regulating myogenesis, hypertrophy, and atrophy. We contrast this success in fundamental biology with the study of myopathies, which remains largely descriptive. Here, a wealth of transcriptomic data has identified dysregulated pathways, including ECM remodeling, metabolism, and inflammation, but functional validation for most candidates is absent. We argue that the critical next step is to apply this established functional genomics toolkit to disease models. By defining causal mechanisms, this research will not only address a major agricultural issue but also provide a model for using genetic tools to dissect complex traits in a post-genomic era. Full article

In an aging society, solving problems associated with the diagnosis and treatment of dementia-related diseases represents a serious challenge. The aim of the study was to evaluate the possibility of applying molecular biology methods to test polymorphisms recognized in the global literature as potentially useful in assessing the risk of developing dementia in a group of patients with hyperlipidemia. A sample of 203 patients: 109 diagnosed with both dementia and hyperlipidemia, 94 with hyperlipidemia, and 101 individuals as an allele frequency control group—were genotyped. Additional data about cognitive decline and neuropsychological assessment were collected. Among all the studied polymorphisms, the frequency of the ABCA1 rs2230806 polymorphism differed between the analyzed groups. The GG genotype (p = 0.0002, RR = 3.22, CI = 1.63 ÷ 6.37) and the G allele (p = 0.0007, RR = 1.53, CI = 1.19 ÷ 1.97) were more frequent in patients diagnosed with dementia, specifically in those with Alzheimer’s disease. Furthermore, the GG genotype was more common in individuals with a shorter disease duration and lower scores on the Montreal Cognitive Assessment (MoCA) scale, and consequently, with greater cognitive function deficits during early stages of the diagnostic process. ABCA1 rs2230806 genotyping is a potential marker for the early identification of dementia risk in patients with hyperlipidemia, which supports the validity of exploring options for incorporating diagnostics based on molecular biology methods. Full article

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide’s potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic–hormonal therapy capable of modifying the natural course of lipedema. Full article

Atopic dermatitis (AD) is a multifactorial skin disorder characterized by immune and barrier dysfunction. The gut–skin axis is a bidirectional pathway through which gut and skin influence each other via microbial metabolites. Bioactive metabolites produced by microbial transformation of phytochemicals show potential for AD prevention. This study developed a computational systems biology pipeline that prioritized gut-derived metabolites from Philippine medicinal plants by integrating metabolite prediction, pharmacokinetics, network analysis, and molecular simulations. From 2231 predicted metabolites, 31 satisfied pharmacological criteria and were mapped to 199 AD-associated targets, with ALB, CASP3, and PPARG identified as hub genes. Two metabolites, THPOC and PM38, exhibited complementary target affinities and strong binding stability. THPOC stabilized ALB and CASP3, supporting barrier integrity and apoptosis regulation, while PM38 strongly engaged PPARG, modulating lipid metabolism and anti-inflammatory transcription. They exhibited comparable or superior docking scores, stable MD interactions, and favorable binding free energies, compared to abrocitinib, an approved AD treatment. DFT analysis confirmed electronic stability and donor–acceptor properties linked to target selectivity. These findings highlight THPOC and PM38 as promising immunometabolic modulators acting on key AD-related pathways. Collectively, this study introduces a reproducible systems-based computational discovery framework, offering a novel preventive strategy for AD. Full article

Skeletal muscle dysfunction is a major systemic manifestation of COPD that shapes symptoms, exercise tolerance and mortality. Current evidence can be integrated within a Damage–Regeneration–Remodeling framework linking mechanics and biology to clinical phenotypes. Pulmonary hyperinflation and chest wall geometry chronically load the diaphragm and other respiratory muscles in COPD, whereas inactivity and exacerbation-related disuse underload locomotor muscles. Across muscle compartments, oxidative/nitrosative stress, activation of proteolytic pathways, mitochondrial and endoplasmic reticulum stress, microvascular limitations, neuromuscular junction instability, and myosteatosis degrade muscle quality. The diaphragm adapts with a fast-to-slow fiber shift, greater oxidative capacity, and sarcomere foreshortening, improving endurance, whereas limb muscles show atrophy, a glycolytic shift, reduced oxidative enzymes, extracellular matrix accrual, and fat infiltration. Translational levers that address these mechanisms include: (I) Reduce damage: bronchodilation, lung-volume reduction, oxygen, non-invasive ventilation, early mobilization, pulmonary rehabilitation, neuromuscular stimulation, and corticosteroid stewardship; (II) Enable regeneration: progressive resistance plus high-intensity/heavy-load endurance training; adequate protein and vitamin-D intake, and endocrine correction; and (III) Steer remodeling: increase physical activity (with/without coaching/telecoaching), functional assessment and CT or MRI monitoring, inspiratory-muscle training, and phenotype-guided adjuncts in selected cases. This framework clarifies why lung deflation strategies benefit inspiratory mechanics, whereas limb recovery requires behavioral and metabolic interventions layered onto systemic optimization. Full article

Food is a crucial component affecting the health of individuals, which may have the potential to expand lifespan. It has been shown that a long lifespan may be related to fine-tuned autophagy. In general, suitable autophagy could play a significant role in the anti-aging biological exertion of the host. AMPK, a member of serine and threonine kinases, could play vital roles within the autophagy signaling pathway in various cells. In addition, alterations in the kinase activity of AMPK have been shown to be connected to several pathologies of aging-related diseases. Therefore, autophagy could control the lifespan-related homeostasis within the host from cells to a body via the modification of AMPK. The design of the diet and/or nutrition targeting the AMPK would be a possibility to expand the lifespan. Some analyses of the molecular biology underlying the autophagy suggest that supplementation of accurate nutraceuticals, as well as dietary restriction, mild fasting, and/or appropriate physical exercise, could modulate AMPK signaling, which may be advantageous for life extension with the alteration of autophagy. Remarkably, it has been revealed that several non-coding RNAs (ncRNAs) might also play significant roles in the regulation of autophagy. In addition, the production of some ncRNAs may be associated with the alteration of gut microbiota with certain diets. Therefore, the modulation of AMPK action with ncRNAs through choosing the relevant diet could be a therapeutic tactic for promoting longevity, which is also accompanied by a reduced risk for several aging-related diseases. Full article

Breast cancer is the most common malignancy in women, with the Luminal A subtype generally associated with favorable survival. However, age and menopausal status may influence tumor biology and prognosis. To improve prediction beyond conventional models, we analyzed transcriptomic and clinical data from the METABRIC cohort. Patients with Luminal A breast cancer were stratified into premenopausal, postmenopausal–nongeriatric, and geriatric (≥70 years) groups. Differentially expressed genes (DEGs) were identified, and Boruta feature selection revealed 27 clinical and genomic variables. Random Forest, Logistic Regression, Multilayer Perceptron, and ensemble XGBoost models were trained with stratified 5-fold cross-validation, using SMOTE to correct class imbalance. Principal component analysis showed distinct clustering across age groups, while DEG analysis revealed 41 genes associated with age and survival. Key predictors included clinical variables (age, tumor size, NPI, radiotherapy) and molecular markers (ATM, HERC2, AKT2, FOXO3, CYP3A43). Among ML models, XGBoost demonstrated the highest performance (accuracy 98%, sensitivity 98%, specificity 97%, F1-score 0.99, AUC 0.86), outperforming other algorithms. These findings indicate that age-related transcriptomic changes impact survival in Luminal A breast cancer and that an ML-based integrative approach combining clinical and molecular variables provides superior prognostic accuracy, supporting its potential for clinical application. Full article

Background: Various thiolactones are known as biologically active compounds, capable of stimulating the development of several human diseases and quorum sensing of Gram–positive bacteria. The enzymatic hydrolysis of thiolactones represents a promising approach to preventing their action. Methods: Thirteen enzymes, including various lactonases and serine hydrolases were studied in this work using several substrates including the homocysteine thiolactone (HTL), and its derivatives the N–acetylhomocysteine thiolactone (C₂–HTL) and the isobutyryl–homocystein thiolactone (i–but–HTL). The potential interactions of the ligands with the surface of enzymes molecules were predicted in silico using computational modeling and checked in wet experiments in vitro. Results: Based on the data obtained several enzymes were selected with localization of the thiolactones near their active sites, indicating the possibility of effective catalysis. The lactonase (AiiA), metallo-β-lactamase (NDM-1) and the organophosphate hydrolase with hexahistidine tag (His₆–OPH) were among them. Determination of catalytic characteristics of enzymes in the hydrolytic reactions with the HTL and the C₂–HTL revealed the maximal value of catalytic efficiency constant for the NDM-1 in the hydrolysis of the HTL (826 M⁻¹ s⁻¹). The maximal activity in the hydrolysis of C₂–HTL was established for AiiA (137 M⁻¹ s⁻¹). The polyaspartic (PLD₅₀) and the polyglutamic (PLE₅₀) acids were used to obtain polyelectrolyte complexes with enzymes. The further combination of these complexes with the clotrimazole and polymyxin B possessing antimicrobial properties resulted in notable improvement of their action in relation to Staphylococcus cells. Conclusions: It was revealed that the antimicrobial activity of the polymyxin B is enhanced by 9–10 times against bacteria and yeast when combined with the His₆–OPH polyelectrolyte complexes. The antimicrobial activity of clotrimazole was increased by ~7 times against Candida tropicalis cells in the case of the AiiA/PLE₅₀/Clotrimazole combination. These results make the obtained biology attractive and promising for their further advancement to practical application. Full article

Mesenchymal chondrosarcoma (MCS) is characterised by small round cell biology, frequent HEY1-NCOA2 fusion, and high vascularity. These features plausibly lessen extracellular matrix barriers and confer relative chemosensitivity. We synthesised peri-operative (preoperative/neoadjuvant; postoperative/adjuvant) and palliative chemotherapy outcomes separately across multiple cohorts and case reports as well as the summarised the guidelines (ESMO/NCCN) In localised disease, integrating multi-agent Ewing-type chemotherapy with complete resection is associated with improved disease control. Contemporary 5-year overall survival (OS) typically spans ~55–73% across studies, while event-free survival (EFS) gains are demonstrated more consistently than OS gains in pooled analyses. In advanced MCS, first-line polychemotherapy yields modest, non-curative activity, with objective response rates (ORRs) of ~25–35% in adults, median progression-free survival (PFS) of ~4.7–6.7 months, and median OS of ~18 months. Activity may be higher in younger patients and for platinum–anthracycline combinations. We also discussed emerging therapies. Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation. Full article

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms. Full article

Phenomena from a variety of disciplines, including biology, computer science and sociology, can be modeled by graph dynamics in which nodes are associated with states and the node-state association changes in time. Although general k-state dynamics have been considered, most of the research in this area refers to binary dynamics especially as far as deterministic dynamics are regarded. In this paper 3-state deterministic dynamics are studied from the computational complexity perspective. A tractability result is proved when the third state is a state of neutrality, adopted by any node unable to establish a preference between the two remaining states. Subsequently, two hardness results are proved for two cases where each of the three states represents a semantically distinct state: the case in which a state change occurs in a node only if the most preferred state among the remaining two receives a suitable number of preferences, and the case in which a state change occurs in a node only if its current state lacks sufficient preferences and the most preferred state among the remaining two receives a suitable number of preferences. Finally, the relation of the last two results and a conjecture from the 1980s is discussed and it is shown that the conjecture is contradicted in both cases. Full article

Background: Methotrexate (MTX) is the most used anti-rheumatic drug for the treatment of early rheumatoid arthritis (ERA) patients, with an adequate response rate of only 30–40%. Thus, early detection of response failure is very crucial to prevent permanent disability. Objectives: We aimed to provide an update on the current evidence of potential predictive biomarkers of MTX treatment response (MTX-TR) in patients with ERA. Materials and Methods: PubMed/MEDLINE, Scopus, EBSCO, and Cochrane Library were searched for studies that investigated a multitude of predictive metabolites of MTX-TR in ERA patients during the 2000–2024 period. This study was registered in PROSPERO (ID: CRD42024547651). Results: We determined that 31 out of 102 metabolites studied were the best predictive of MTX-TR in ERA, using clinical response (DAS28-ESR score). Our results on serum protein profiles revealed that higher pre-treatment levels of myeloid-related proteins, MTX–polyglutamates, choline, inosine, hypoxanthine, guanosine, nicotinamide, and diglyceride, and lower pre-treatment levels of N-methyl isoleucine, 2,3-dihydroxy butanoic acid, nor-nicotine, glucosylceramide, and itaconic acid, were associated with a good MTX-TR. However, lower baseline plasma itaconate and its derivatives and haptoglobin, but a higher baseline level of galactosylated glycans (FA2G) of IgG1, were associated with a good response to MTX. The results on immune cell biology indicated that higher pre-treatment of regulatory B cells, lower pre-treatment of Treg, and RDW were correlated with a good MTX-TR. The results on inflammatory biomarkers showed that a lower IL-1ra/IL1B ratio and IL-6 levels after MTX indicated a good response. Conclusions: This study provides an update on the current evidence of the potential predictive metabolites for the best MTX-TR in ERA patients. We revealed that few biomarkers resulted in a remission state of patients with ERA. These biomarkers are promising but not yet ready for routine clinical use; they warrant validation in larger prospective trials. We recommend that, for the implementation of personalized medicine, these biomarkers should be the first-line biomarkers for use in routine clinical practice after validation. Full article

Lumpy Skin Disease Virus (LSDV), a member of the poxvirus family, represents a significant threat to global cattle industries. This review presents an analysis of LSDV-encoded proteins and their interactions with host systems, elucidating the molecular mechanisms governing viral life cycle progression and immune evasion strategies. We provide detailed characterization of the complex architecture of LSDV virions, including Intracellular Mature Virus (IMV), Extracellular Enveloped Virus (EEV), lateral bodies, and the core components, while summarizing the crucial functions of viral proteins throughout various stages of infection—entry, replication, transcription, translation, assembly, and egress. Particular attention is given to the immunomodulatory strategies employed by LSDV to subvert both innate and adaptive immune responses. These mechanisms encompass molecular mimicry of cytokines and chemokines, interference with antigen presentation pathways, inhibition of key immune signaling cascades, and modulation of apoptosis and autophagy processes. Through comparative analysis with homologs from related poxviruses, especially vaccinia virus, we highlight both evolutionarily conserved functions and potential unique adaptations in LSDV proteins. This review further identifies critical knowledge gaps in current understanding and proposes promising research directions. We emphasize that integrating multi-omics approaches with structural biology will be essential for advancing our understanding of LSDV pathogenesis and for developing novel preventive and therapeutic strategies against this important animal pathogen. Full article