Search Results (7,486)

Background/Objectives: Myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic disorder characterized by ineffective hematopoiesis and leukemic transformation risk. Current therapies show limited efficacy, with ~50% of patients failing hypomethylating agents. This review aims to synthesize recent discoveries through an integrated network model and examine translation into precision therapeutic approaches. Methods: We reviewed breakthrough discoveries from the past three years, analyzing single-cell multi-omics technologies, epitranscriptomics, stem cell architecture analysis, and precision medicine approaches. We examined cell-type-specific splicing aberrations, distinct stem cell architectures, epitranscriptomic modifications, and microenvironmental alterations in MDS pathogenesis. Results: Four interconnected mechanisms drive MDS: genetic alterations (splicing factor mutations), aberrant stem cell architecture (CMP-pattern vs. GMP-pattern), epitranscriptomic dysregulation involving pseudouridine-modified tRNA-derived fragments, and microenvironmental changes. Splicing aberrations show cell-type specificity, with SF3B1 mutations preferentially affecting erythroid lineages. Stem cell architectures predict therapeutic responses, with CMP-pattern MDS achieving superior venetoclax response rates (>70%) versus GMP-pattern MDS (<30%). Epitranscriptomic alterations provide independent prognostic information, while microenvironmental changes mediate treatment resistance. Conclusions: These advances represent a paradigm shift toward personalized MDS medicine, moving from single-biomarker to comprehensive molecular profiling guiding multi-target strategies. While challenges remain in standardizing molecular profiling and developing clinical decision algorithms, this systems-level understanding provides a foundation for precision oncology implementation and overcoming current therapeutic limitations. Full article

Agrarian women are at the forefront of rural livelihoods increasingly affected by the frequency and severity of climate change impacts. However, their household livelihood resilience (HLR) remains limited due to gender-blind policies, scarce sex-disaggregated data, and inadequate consideration of gender-specific needs in resilience-building efforts. Grounded in participatory feminist research, this study employed a multi-method qualitative approach, including semi-structured interviews and oral history narratives, with 60 women in two climate-vulnerable provinces. Data were analyzed through thematic coding, CATWOE (Customers, Actors, Transformation, Worldview, Owners, Environmental Constraints) analysis, and descriptive statistics. The findings identify nine major climate-related events disrupting livelihoods and reveal a limited understanding of HLR as a long-term, transformative concept. Adaptation strategies remain short-term and focused on immediate survival. Barriers to HLR include financial constraints, limited access to agricultural resources and technology, and entrenched gender norms restricting women’s leadership and decision-making. While local governments, women’s associations, and community networks provide some support, gaps in accessibility and adequacy persist. Participants expressed the need for financial assistance, vocational training, agricultural technologies, and stronger peer networks. Strengthening HLR among agrarian women requires gender-sensitive policies, investment in local support systems, and community-led initiatives. Empowering agrarian women as agents of change is critical for fostering resilient rural livelihoods and achieving inclusive, sustainable development. Full article

Several natural products have been shown to display antiviral activity against the hepatitis B virus (HBV), among a number of other viruses. In a previous study, the hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest were tested on the hepatoma cell line HepG2.2.15, which constitutively produces HBV. One of the species that exerted inhibitory activity on HBV replication was Senna silvestris. The aim of this study was the bioassay-guided purification of the ethanol fraction of leaves of S. silvestris, which displayed the most significant inhibitory activity against HBV. After solvent extraction and two rounds of reverse-phase HPLC purification, NMR analysis identified salsolinol as the compound that may exert the desired antiviral activity. The purified compound exerted inhibition of both HBV DNA and core HBV DNA. Pure salsolinol obtained from a commercial source also displayed anti-HBV DNA inhibition, with an approximate MIC value of 12 µM. Although salsolinol is widely used in Chinese traditional medicine to treat congestive heart failure, it has also been associated with Parkinson’s disease. More studies are warranted to analyze the effect of changes in its chemical conformation, searching for potent antiviral, perhaps dual agents against HBV and HIV, with reduced toxicity. Full article

The genotoxin colibactin, a complex secondary metabolite, targets eukaryotic cell cycle machinery and contributes to neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) XM, which produces this genotoxin, is an agent of poultry diseases with zoonotic potential. In this study, we confirmed that clbF was necessary for the APEC XM strain to produce colibactin, but it did not affect the growth, adhesion, or invasion of cells. Deletion of clbF substantially diminished both virulence and systemic dissemination, but it also changed the gene expression of the antiserum survival factor, adherence and invasion, iron acquisition genes, and the secretion system. In conclusion, clbF is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice. Full article

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article

Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial–mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma. Full article

Climbing vines have recently induced increasing threats to forest growth under favourable environmental changes. In mangrove forests, the native vine Derris trifoliata became invasive and is now one of the main threats. Yet current management relies on manual removal with low efficiency. Exploring an alternative, cost-effective method is required. To assess the potential of a proposed biological control method, this study performed a pot-plant experiment using Cuscuta japonica to infect D. trifoliata and three common mangrove species in Beihai, China. Results showed that D. trifoliata had a higher infection rate and high host mortality (90%) than mangrove (0%). It also had significantly decreased moisture by 4%, nitrogen by 14%, phosphorus by 27%, potassium by 49% and increased soluble sugar by 49% and protein by 20%, whereas only moisture (2% reduction) and one or two minerals of Excoecaria agallocha and Aegiceras corniculatum were influenced. Only Kandelia obovata had neither effective haustoria nor any nutrients impact from the infection. This study indicated that C. japonica can cause more damage to D. trifoliata than to mangrove species and has the potential to be used as a biological control agent for the threatened mangrove forests of A. corniculatum and K. obovata with monitoring and control. Further field tests are required to bring this method into practice. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a health related threat world-wide. Biosynthesized gold nanoparticles (AuNPs) using plant extracts have been reported to exhibit certain biological activity. This study aimed to biosynthesize AuNPs using an aqueous extract of Eruca sativa leaves and to evaluate their biocompatibility, antimicrobial activity, and antioxidant properties. Methods: AuNPs were biosynthesized using an aqueous extract of Eruca sativa leaves. Their biocompatibility was evaluated through hemolytic activity and assessments of hepatic and renal functions in rats. AuNPs were biologically evaluated as antimicrobial and antioxidant agents. Results: The AuNPs exhibited particle sizes of 27.78 nm (XRD) and 69.41 nm (AFM). Hemolysis assays on red blood cells revealed negligible hemolytic activity (<1%). Hepatic enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were studied. ALT, AST, and ALP levels showed no significant changes compared to the negative control. However, LDH levels were elevated at higher concentration (52.8 µg/mL), while the lower concentration (26.4 µg/mL) appeared to be safer. Renal biomarkers, urea and creatinine, showed no significant changes at either concentration, indicating minimal nephrotoxicity. The antimicrobial activity of AuNPs, plant extract, and gold salt was tested against five microorganisms: two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and a fungal strain (Candida albicans). The AuNPs exhibited minimum inhibition concentrations (MICs) of 13.2 µg/mL against S. aureus and S. pneumoniae, 26.4 µg/mL against E. coli and C. albicans, and 39.6 µg/mL against P. aeruginosa, suggesting selectivity towards Gram-positive bacteria. Furthermore, the AuNPs demonstrated strong antioxidant activity, surpassing that of vitamin C. Conclusions: The biosynthesized AuNPs exhibited promising biocompatibility, selective antimicrobial properties, and potent antioxidant activity, supporting their potential application in combating the AMR. Full article

Ozone is a powerful destructive agent in the oxidative process of polymer composites. The destructive ability of ozone depends primarily on its concentration, duration of exposure, the type of polymer, and its matrix structure. In this work, nonwoven PLA/NR fibers with natural rubber contents of 5, 10, and 15 wt.% were obtained, which were then subjected to ozone oxidation for 800 min. The effect of ozone treatment was estimated using various methods of physicochemical analysis. The visual effect was manifested in the form of a change in the color of PLA/NR fibers. The method of differential scanning calorimetry revealed a change in the thermophysical characteristics. The glass transition and cold crystallization temperatures of polylactide shifted toward lower temperatures, and the degree of crystallinity increased. It was found that in PLA/NR fiber samples, the degradation process predominates over the crosslinking process, as an increase in the melt flow rate by 1.5–1.6 times and a decrease in the correlation time determined by the electron paramagnetic resonance method were observed. The IR Fourier method recorded a change in the chemical structure during ozone oxidation. The intensity of the ether bond bands changed, and new bands appeared at 1640 and 1537 cm⁻¹, which corresponded to the formation of –C=C– bonds. Full article

Background and Objectives: Anesthetic agents may influence brain function, and emerging evidence suggests possible neurotoxicity under certain conditions. S100β is a well-established biomarker of brain injury and blood–brain barrier disruption, and its prolonged elevation beyond 6–12 h, despite a short half-life, may indicate ongoing neuronal injury. Its use in cesarean section (C-section) remains limited, despite the potential neurological implications of both surgical stress and anesthetic technique. This study evaluates potential brain injury during caesarean section by comparing maternal and neonatal S100β levels under general and spinal anesthesia. Materials and Methods: This observational prospective study compared changes in the S100β brain damage biomarker in maternal (pre- and post-surgery) and umbilical artery blood during elective c-sections under general or spinal anesthesia. The 60 parturient women who underwent a C-section from 1 July 2021 to 30 December 2023 were evenly distributed into 2 groups: General anesthesia (GA) (n = 30) and Spinal anesthesia (SA) group (n = 30). It included healthy term pregnant women aged 18–40, ASA I–II and excluded those with major comorbidities or emergency conditions. Results: S100β concentrations slightly increased once the C-section was over in both the SA and GA groups, but without notable differences. In the SA and GA groups, preoperative S100β concentration in maternal blood was 195.1 ± 36.2 ng/L, 193.0 ± 54.3 ng/L, then increased to 200.9 ± 42.9 ng/L, 197.0 ± 42.7 at the end of operation. There was no statistically significant difference in S100β concentrations between the spinal and general anesthesia groups (p = 0.86). Conclusions: S100β concentrations slightly increased after C-section in both groups. The form of anesthesia seems to be irrelevant for the S100β level. However, further research is needed to confirm these findings and fully evaluate any potential long-term effects. Full article

Poliovirus represents an oncolytic agent for human glioblastoma—one of the most aggressive types of cancer. Since interference of viruses with metabolic and redox pathways is often linked to their pathogenesis, drugs targeting metabolic enzymes are regarded as potential enhancers of oncolysis. Our goal was to reveal an imprint of poliovirus on the metabolism of glioblastoma cell lines and to assess the dependence of the virus on these pathways. Using GC-MS, HPLC, and Seahorse techniques, we show that poliovirus interferes with amino acid, purine and polyamine metabolism, mitochondrial respiration, and glycolysis. However, many of these changes are cell line- and culture medium-dependent. 2-Deoxyglucose, the pharmacologic inhibitor of glycolysis, was shown to enhance the cytopathic effect of poliovirus, pointing to its possible repurposing as an enhancer of oncolysis. Inhibitors of polyamine biosynthesis, pyruvate import into mitochondria, and fatty acid oxidation exhibited antiviral activity, albeit in a cell-dependent manner. We also demonstrate that poliovirus does not interfere with the production of superoxide anions or with levels of H₂O₂, showing an absence of oxidative stress during infection. Finally, we showed that a high rate of poliovirus replication is associated with fragmentation of the mitochondrial network, pointing to the significance of these organelles for the virus. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Based on recent work outlining the transformation of professional communicator roles and the desperate search for “curators” or “agents of change” in neighboring disciplines such as management, business and economics, sustainability studies and education, we present a systematic reflection of concepts in higher education for sustainability and their (missing) fit to professional communication education in a world in crisis. The blind spots and challenges identified, especially from a communication perspective, will be filled with concepts from environmental communication pedagogy, pointing to the need for more participatory strategies and radicality in professional communication education. Concrete modalities of instruction will be discussed and supported by eight reconstruction interviews with pedagogues, educators and students from diverse cultural contexts involved in sustainability communication education. The findings show the need for more radical pedagogy and unorthodoxy. The paper finishes with suggestions for practices that materialize sustainability in co-created sites of change. Full article