Search Results (7,670)

Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 GBC to guide practice and research. Methods: This narrative review synthesizes recent literature on surgical management of Tis, T1a, T1b, and T2 GBC based on American Joint Committee on Cancer (AJCC) 8th edition staging. It examines simple vs. extended cholecystectomy (simple cholecystectomy (SC) vs. extended/radical cholecystectomy (EC/RC)), the role of lymphadenectomy (LND) and hepatectomy, and minimally invasive surgery (MIS). Results: Simple cholecystectomy is curative for Tis/T1a GBC. For T1b, regional LND is essential for staging/potential benefit, especially examining ≥5–6 nodes. Tumor size is critical; SC alone may suffice for T1b < 1 cm (low lymph node metastasis (LNM) risk), while EC/RC with LND is indicated for ≥1 cm (higher LNM risk). Routine hepatectomy for T1b lacks survival support. For T2 GBC, mandatory regional LND (≥6 nodes) is required for both T2a and T2b substages due to high LNM rates; T2b has higher LNM than T2a. Routine hepatectomy for T2 is debated; evidence suggests no routine benefit for T2a beyond LND, with conflicting findings for T2b. R0 resection is paramount. MIS is feasible for early stages in experienced hands. Conclusions: Management of early GBC is moving towards risk stratification. SC is standard for Tis/T1a. Adequate regional LND is crucial for T1b (especially ≥1 cm) and mandatory for T2 GBC. Routine hepatectomy, particularly for T2b, remains controversial. Tailored surgery prioritizes R0 resection and comprehensive LND, necessitating further standardized research. Full article

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article

Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways. Combined with weighted gene co-expression network analysis (WGCNA) and RT-qPCR validation, five candidate genes (WRKY6, WRKY70, NHX1, AVP1, and NAC072) were identified as the regulators of salt tolerance in rapeseed. Haplotype analysis based on association mapping showed that NAC072, ABI5, and NHX1 exhibited two major haplotypes that were significantly associated with salt tolerance variation under salt stress in rapeseed. Integrated miRNA-mRNA analysis and RT-qPCR identified three regulatory miRNA-mRNA pairs (bna-miR160a/BnaA03.BAG1, novel-miR-126/BnaA08.TPS9, and novel-miR-70/BnaA07.AHA1) that might be involved in S268 salt tolerance. These results provide novel insights into the post-transcriptional regulation of salt tolerance in B. napus, offering potential targets for genetic improvement. Full article

Background: Autism spectrum disorder (ASD) represents a neurobiological disorder with a high prevalence in the children’s population. The aim of the present review was to assess the current evidence on the use of salivary biomarkers for the early diagnosis of ASD. Materials and methods: A search was conducted on the electronic databases PUBMED/Medline, Google Scholar and Scopus for the retrieval of articles concerning the study topic. Results: A total of 22 studies have been included in the present review considering 21 articles identified from databases and 1 article included using a manual search. A wide range of biomarkers have been proposed for early detection of ASD diseases including nonspecific inflammation markers like interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), oxidative stress markers like superoxide dismutase and glutathione peroxidase, hormones such as cortisol and oxytocin, various microRNAs including miR-21, miR-132 and miR-137, and exosomes. The techniques used for biomarke detection may vary according to molecule type and concentration. Conclusions: salivary biomarkers could represent a potential useful tool for the primary detection of several systemic diseases including ASD, taking advantage of non-invasiveness and cost-effective capability compared to other biofluid-based diagnostic techniques. Full article

Amylose content significantly influences the technological, quality, and nutritional properties of starchy foods. This study developed a rapid, non-destructive method to quantify amylose content in starch using mid-infrared (MIR) spectroscopy combined with chemometric techniques. Manually prepared starch mixtures with varying amylose levels were scanned to obtain MIR spectra, which were preprocessed using smoothing and z-score normalization to reduce operational variability. Three variable selection methods, including bootstrap soft shrinkage (BOSS), competitive adaptive reweighted sampling (CARS), and uninformative variable elimination (UVE), were applied to select the useful spectra. A partial least square (PLS) model was then constructed to correlate selected spectral data with amylose content. The results revealed that the number and position of selected variables differed across different optimization methods, which influenced the model’s performance. It is worth noting that the optimized PLS model significantly reduced the root mean squared error of cross-validation (RMSECV) and improved prediction accuracy in 50 runs. In particular, the CARS-PLS model showed superior performance, achieving a correlation coefficient (R_p) of 0.964 and a root mean squared error of prediction (RMSEP) of 4.59, a 60% improvement over the original PLS model, which had an RMSEP of 11.56. These results highlight MIR spectroscopy’s potential, combined with optimized chemometric models, for accurate amylose quantification in food quality control. Full article

This study evaluated the effectiveness of eDNA metabarcoding in assessing fish communities in two urban lakes (First Lake and Second Lake) in Zagreb, Croatia, following IAS removal. Water samples were collected in April and June 2024 and analyzed using MiFish primers targeting the 12S rRNA gene. The results indicated that the cleanup efforts were largely successful, as several IAS previously recorded in these lakes were not detected (Ameiurus melas, Lepomis gibbosus, and Hypophthalmichthys spp.). However, some others persisted in low relative abundances, such as grass carp (Ctenopharyngodon idella), topmouth gudgeon (Pseudorasbora parva), and prussian/crucian carp (Carassius sp.). Species composition differed between lakes, with common carp (Cyprinus carpio) dominating Maksimir First Lake, while chub (Squalius cephalus) was prevalent in Maksimir Second Lake. Unexpected eDNA signals from salmonid and exotic species suggest potential input from upstream sources, human activity, or the nearby Zoo Garden. These findings underscore the utility of eDNA metabarcoding in biodiversity monitoring and highlight the need for continuous surveillance and adaptive management strategies to ensure long-term IAS control. Full article

We report a case of catheter-associated bloodstream infection caused by a putative novel species in the genus Erwinia, identified using whole-genome sequencing (WGS). A female adolescent receiving long-term home parenteral nutrition via a central venous catheter (CVC) presented with a fever. Gram-negative rods were isolated from two CVC-derived blood culture sets, while peripheral cultures remained negative. Conventional identification methods, including VITEK 2, Phoenix M50, MALDI-TOF MS, and 16S rRNA and rpoB gene sequencing, failed to achieve species-level identification. WGS was performed on the isolate using Illumina MiSeq. Genomic analysis revealed a genome size of 5.39 Mb with 56.8% GC content and high assembly completeness. The highest average nucleotide identity (ANI) was 90.3% with Pantoea coffeiphila, and ≤85% with known Erwinia species, suggesting that it represents a distinct taxon. Phylogenetic analyses placed the isolate within the Erwinia clade but separate from any known species. Antimicrobial susceptibility testing showed broad susceptibility. This case highlights the utility of WGS for the identification of rare or novel organisms not captured by conventional methods and expands the clinical spectrum of Erwinia species. While the criteria for species delineation were met, the phenotypic characterization remains insufficient to formally propose a new species. Full article

Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in patients with NAFLD and find out if they are related to any clinical factors. Subjects and Methods: Thirty-eight age-matched healthy persons and thirty-eight NAFLD patients were enrolled. Patients were split into the following three groups: non-alcoholic steatohepatitis (NASH) (n = 12), patients with NAFLD-related cirrhosis (n = 8), and patients with NAFLD-related simple steatosis (n = 18). Real-time PCR was utilized to examine the expression. Results: The lncRNA GAS5 and NOTCH2 were higher in NAFLD cases in comparison to controls. On the other hand, microRNA-29a-3p was underexpressed in NAFLD cases in comparison to controls. Regarding NAFLD diagnosis, lncRNA GAS5 was the best single marker with a sensitivity of 100% and a specificity of 94.7% at the cutoff values of ≥1.16-fold change. Regarding different stages of the disease, the highest level of lncRNA GAS5 was in cirrhosis. lncRNA GAS5 expression, among other studied parameters, is still a significant predictor of NAFLD (adjusted odds ratio of 162, C.I. = 5.7–4629) (p = 0.003). LncRNA GAS5 has a positive correlation with NOTCH2 and a negative correlation with miR-29a-3p. LncRNA GAS5, NOTCH2, and RNA-29a-3p were significantly different in NAFLD cases compared to controls. Conclusions: lncRNA GAS5 appears to be the most effective single marker for detecting NAFLD. LncRNA GAS5 expression is a significant independent predictor of NAFLD. LncRNA GAS5 can differentiate different NAFLD stages. Full article

MicroRNA-211 (miR-211) is a versatile regulatory molecule that plays critical roles in cellular homeostasis and disease progression through the post-transcriptional regulation of gene expression. This review comprehensively examines miR-211’s multifaceted functions across various biological systems, highlighting its context-dependent activity as both a tumor suppressor and oncogene. In physiological contexts, miR-211 regulates cell cycle progression, metabolism, and differentiation through the modulation of key signaling pathways, including TGF-β/SMAD and PI3K/AKT. miR-211 participates in retinal development, bone physiology, and protection against renal ischemia–reperfusion injury. In pathological conditions, miR-211 expression is altered in various diseases, particularly cancer, where it may be a useful diagnostic and prognostic biomarker. Its stability in serum and differential expression in various cancer types make it a promising candidate for non-invasive diagnostics. The review also explores miR-211’s therapeutic potential, discussing both challenges and opportunities in developing miRNA-based treatments. Understanding miR-211’s complex regulatory interactions and context-dependent functions is crucial for advancing its clinical applications for diagnosis, prognosis, and targeted therapy in multiple diseases. Full article

Wound healing is a complex and dynamic process involving several stages of tissue repair. This study has shown that extracellular vesicles (EVs) derived from the callus of Camellia japonica L. and their associated microRNAs (miRNAs) possess significant wound healing activities. In human fibroblasts, EVs from C. japonica L. stimulated wound healing and upregulated collagen gene expression. The EVs also decreased inflammation levels in human keratinocytes, supporting wound healing. Among the miRNAs identified, miR408, one of the abundant miRNAs in the EVs, also showed similar wound healing efficacy. These findings suggest that both EVs and miR408 from the callus of C. japonica L. play a pivotal role in promoting wound healing. Additionally, this study shows that the regulation of miRNAs between different kingdoms can be achieved and suggests a new direction for the utilization of plant-derived components. Full article

Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and fibrotic outcomes in the lens remains unclear. Here, we used an ex vivo chick lens injury model to simulate post-surgical conditions, collecting RNA from lenses undergoing either regenerative wound healing or fibrosis between days 1–3 post-injury. Bulk RNA sequencing data were normalized, log-transformed, and subjected to univariate filtering prior to training LASSO, SVM, and RF ML models to identify discriminatory gene signatures. Each model was independently validated using a held-out test set. Distinct gene sets were identified, including fibrosis-associated genes (VGLL3, CEBPD, MXRA7, LMNA, gga-miR-143, RF00072) and wound-healing-associated genes (HS3ST2, ID1), with several achieving perfect classification. Gene Set Enrichment Analysis revealed divergent pathway activation, including extracellular matrix remodeling, DNA replication, and spliceosome associated with fibrosis. RT-PCR in independent explants confirmed key differential expression levels. These findings demonstrate the utility of supervised ML for discovering lens-specific fibrotic and regenerative gene features and nominate biomarkers for targeted intervention to mitigate PCO. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Metasurfaces have drawn extensive research attention for their unique optical properties and vast application potential. Among the various resonant modes induced in metasurfaces, BIC and electric anapole modes stand out as particularly interesting due to their distinctive physical characteristics. In this work, we designed and investigated novel dimeric dumbbell-shaped metasurfaces incorporating two independently tunable asymmetric parameters. This structural innovation enables the simultaneous excitation of both electric anapole and QBIC modes under normally incident MIR illumination. More importantly, by adjusting these two asymmetric parameters, one can independently tune the resonance peaks of the two modes, thereby overcoming the performance limits of conventional single-peak modulation. This metasurface design demonstrates outstanding performance for dielectric environment-sensing applications. We conducted a comprehensive investigation of the sensing sensitivity for dumbbell-shaped metasurfaces of various geometries. Our simulation results show that the circular-shaped configuration achieved high sensitivity, reaching 20,930 GHz/RIU. This work offers a novel design paradigm for multi-mode control and functionalization of metasurface structures. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article