Search Results (1,003)

Background: The treatment of cavitated lesions has evolved with minimally invasive dentistry (MID), whereby we can leave demineralized enamel that could potentially be remineralizable with the use of materials such as resin-modified glass ionomer cements (RMGICs) that allow these lesions to be repaired and remineralized while removing less tooth tissue. The aim of our study was to compare the influence of aging on adhesion to sound enamel, demineralized enamel, and the healthy dentin of five RMGICs (Vitremer^®, ACTIVA BioACTIVE Restorative, Riva LC, Ionolux^®, and GC Fuji II LC) and fluoride release. There are currently no studies on adhesion in demineralized enamel. Method: A total of 1035 bovine incisors were analyzed in 45 groups of 23 teeth each. The groups were established based on three factors: time (24 h, 1 month, and 3 months); substrate (sound enamel, demineralized enamel, and healthy dentin); and type of material. In each group, 20 samples underwent shear bond strength (SBS) and fracture type analysis. Adhesive interfaces were observed in three samples from each group using field emission scanning electron microscopy (FESEM). Daily and cumulative fluoride release rates were calculated. Results: Adhesion improved over time on both demineralized and sound enamel. ACTIVA BioACTIVE Restorative had the highest SBS values (33.63 ± 10.69 MPa), and Vitremer^® had the lowest (4.10 ± 4.63). Most fractures were adhesive. Vitremer^® and Ionolux^® showed the highest daily and cumulative fluoride release rates (Vitremer daily (24 h): 225.30 ± 26.28 ppm/g; Vitremer cumulative (30 days): 635.99 ± 305.38 ppm/g; Ionolux daily (24 h): 207.59 ± 48.43 ppm/g; Ionolux cumulative (30 days): 501.21 ± 138.71 ppm/g) and ACTIVA BioACTIVE Restorative showed the lowest (ACTIVA daily (24 h): 10.50 ± 0.85; ACTIVA cumulative (30 days): 39.10 ± 2.16). Conclusions: ACTIVA BioACTIVE Restorative was the material with the best adhesion values on all substrates and at all times, but it showed the lowest fluoride release rates. Full article

Background/Objectives: MicroRNAs (miRNAs) regulate gene expression and are proposed as biomarkers in colorectal cancer (CRC). This study evaluated miR-185-5p, miR-141-5p, and miR-21-5p expression in CRC tissues; their association with tumor location, histopathology, and clinical outcomes; and the suitability of miR-16-5p and miR-151a-3p as housekeeping controls. Previous reports suggest tumor-suppressive roles for miR-185 and miR-141 and an oncogenic function for miR-21, though findings remain inconsistent. Methods: Paired tumor and adjacent normal tissues from 70 CRC patients were analyzed. RNA was extracted from FFPE samples, and miRNA expression quantified by RT-qPCR. Relative expression values were normalized to miR-151a-3p. Tumor–normal differences, localization effects, and associations with clinicopathological and outcome variables were assessed using repeated-measures ANOVA and non-parametric tests. Results: miR-185-5p and miR-141-5p were significantly reduced in tumors compared with normal mucosa while miR-21-5p was upregulated. miR-16-5p showed higher expression in normal tissue, indicating its instability and unsuitability as a housekeeping control. A modest but significant localization effect was observed for miR-185, while other miRNAs were minimally influenced by location. Baseline asymmetry between non-tumor samples, observed for miR-185-5p, further indicated sidedness effects. None of the miRNAs were associated with stage, histological type, grade, invasion, immune infiltration, progression, or five-year survival. Conclusions: miR-185-5p, miR-141-5p, and miR-21-5p show robust tumor–normal differences, supporting their diagnostic potential, while miR-16-5p is unsuitable as a housekeeper. Modest but significant localization effect was observed for miR-185 in right-sided tumors. None showed prognostic value in stage I–III CRC. Larger, location-stratified studies are warranted. Full article

Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to fresh-frozen specimens of one HCC and one liver metastasis (>16,000 genes per sample, >97% mapping rates) as a proof-of-principle two-specimen study, cross-validated in human proteomics and patients’ survival datasets. Transcriptional clustering revealed spatially distinct compartments, rare cell states, and pathway alterations, which were further compared against an independent systemic dataset. Results: HCC displayed an ordered lineage architecture, with transformed hepatocyte-like tumor cells broadly dispersed across the tissue and more differentiated hepatocyte-derived cells restricted to localized zones. By contrast, liver metastases showed two sharply compartmentalized domains: an invasion zone, where proliferative stem-like tumor cells occupied TAM-rich boundaries adjacent to hypoxia-adapted tumor-core cells, and a plasticity zone, which formed a heterogeneous niche of cancer–testis antigen–positive germline-like cells. Across both tumor types, we detected a conserved metabolic program of “porphyrin overdrive,” defined by reduced cytochrome P450 expression, enhanced oxidative phosphorylation gene expression, and upregulation of FLVCR1 and ALOX5, reflecting coordinated rewiring of heme and lipid metabolism. Conclusions: In this pilot study, HCC and liver metastases demonstrated fundamentally different spatial architectures, with metastases uniquely harboring a germline/neural-like plasticity hub. Despite these organizational contrasts, both tumor types converged on a shared program of metabolic rewiring, highlighting potential therapeutic targets that link local tumor niches to systemic host–tumor interactions. Full article

Background: Gastric cancer is one of the most prevalent malignancies worldwide and the fourth leading cause of cancer-related mortality. Protein ubiquitination and deubiquitination regulate protein stability as post-translational modifications, playing essential roles in tumorigenesis. Although UCHL1, a deubiquitinating enzyme (DUB), is implicated in the progression of several cancer types, its role in gastric cancer remains unclear. Methods: Kaplan–Meier analysis and gastric cancer patient tissues were used to assess UCHL1 expression. Cell viability assay, colony-forming assay, and transwell migration and invasion assay were performed to evaluate cell growth. Immunoprecipitation and Western blotting analyzed protein expression and interactions. Results: This study demonstrates that UCHL1 expression is markedly upregulated in gastric cancer tissues compared to normal tissues. Elevated UCHL1 expression is associated with poor patient prognosis, supporting its potential role as an oncogenic factor. Reduced UCHL1 expression suppressed cell proliferation, migration, and invasion in gastric cancer cell lines. As the underlying mechanism, we identified CIP2A, a known oncogenic regulator of c-Myc, as a downstream effector of UCHL1. UCHL1 knockdown reduced CIP2A protein levels via deubiquitination, attenuated c-Myc signaling, and decreased expression of key cell cycle regulators. Furthermore, UCHL1 knockdown significantly downregulated cyclin D1 expression, arresting the cell cycle in the G1 phase and inhibiting cell proliferation. Conclusions: Collectively, our findings reveal that UCHL1 promotes gastric cancer progression, highlighting it as a potential therapeutic target. Full article

Objectives: miR-21-5p, miR-145-5p and miR-382-5p have been associated with angiogenesis, which plays a central role in tumor growth and metastasis formation. The aim of the study was to determine whether expression of these three potentially angiogenic miRNAs is related to the lymphatic spread capability of gastric adenocarcinoma and patient survival. Methods: Pathoclinical data of 123 patients who underwent elective gastric resection for adenocarcinoma between 1 August 2006 and 31 December 2013 were retrospectively retrieved. The major concerns were the total number of lymph nodes retrieved, the number of positive nodes, depth of the tumor invasion to the stomach wall, pTNM stage of the disease, Lauren histological tumor type, presence of a mucinous component in the cancer tissue, tumor location in the stomach and survival outcome. The cancer tissues of patients were examined for the expression levels of miR-21-5p, miR-145-5p and miR-382-5p. Results: Elevated hsa-miR-21-5p expression levels and downregulated hsa-miR-145-5p levels were observed in patients with a higher pT stage, lymph node metastasis and advanced pTNM stage. Additionally, hsa-miR-145-5p expression was lower in patients with cardia involvement and a Lauren intestinal-type carcinoma. hsa-miR-382-5p levels were higher in patients with non-mucinous gastric carcinoma. Both hsa-miR-145-5p and hsa-miR-21-5p were predictors of the presence of node metastasis, even when adjusted for pT status. hsa-miR-145-5p was significantly associated with improved survival. hsa-miR-145-5p was significantly associated with an increased probability of surviving 3 years, while increased hsa-miR-21 expression was significantly associated with reduced 3-year survival. All these associations were confirmed in multivariate models, which also included pT and M staging. Conclusions: The upregulation of miR-21-5p and downregulation of miR-145-5p are independent prognostic factors for lymph node metastasis and could serve as specific biomarkers of the lymphatic spread of gastric adenocarcinoma. miR-145-5p downregulation is an independent prognostic factor for overall survival. Full article

Background/Objectives: Rates of degenerative spinal pathology are increasing, driving interest in minimally invasive surgical (MIS) techniques that facilitate faster recovery. Full endoscopic lumbar discectomy (FELD) and biportal endoscopic lumbar discectomy (BELD) offer reduced tissue disruption, but comparative outcomes versus non-endoscopic MIS and optimal patient selection remain unclear. This systematic review examines pre-operative characteristics and post-operative outcomes of endoscopic lumbar microdiscectomy (ELMD) compared to MIS and open techniques. Methods: A PRISMA-guided search of PubMed, Embase, Scopus, and hand searches through 31 September 2024 identified studies on lumbar spinal surgery using endoscopic techniques, restricted to level 1a/b and 2a evidence. Articles were subgrouped by surgery type, with this analysis focusing on ELMD. Data extraction included risk-of-bias assessment, and meta-analysis was performed using multivariate mixed-effects regression. Pre-operative patient characteristics and post-operative outcomes for endoscopic lumbar microdiscectomy (ELMD) were directly compared to both open microdiscectomy and minimally invasive non-endoscopic microdiscectomy (MIS) techniques. Within the ELMD cohort, we further analyzed differences between full endoscopic (FELD) and biportal endoscopic (BELD) approaches, as well as between transforaminal and interlaminar access routes. Results: Of 6891 articles, 5469 unique titles/abstracts were screened, yielding 87 studies (3238 patients) for final synthesis. Compared to open microdiscectomy, ELMD patients were more often male, younger, of lower BMI, and had more comorbidities. They typically presented with shorter symptom duration and predominant radiculopathy. ELMD was performed most at L3–L4 and L4–L5. Post-operatively, ELMD patients had significantly lower VAS Leg Pain scores at 1 day and 1 year and reduced recurrence rates. ELMD was associated with lower recurrence rates and correspondingly lower revision surgery rates, with dural tears and wound infections trending lower compared to open surgery. Compared to non-endoscopic MIS, pre- and post-operative characteristics were similar. BELD patients more often had longer symptom duration, motor weakness, and hyporeflexia than FELD patients. Conclusions: ELMD patients demonstrate favorable pain relief and reduced recurrence versus open surgery, with outcomes comparable to MIS. These findings support ELMD as a less invasive alternative within the MIS spectrum. Full article

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been frequently reported in multiple malignancies, driving oncogenic processes including uncontrolled proliferation, invasion, migration, and metastasis, and correlating with unfavorable clinical outcomes. Their restricted expression in normal tissues, together with their consistent association with poor prognosis across cancer types, highlights their potential as diagnostic biomarkers, therapeutic targets, and prognostic indicators. This review summarizes the structural features and biological functions of the FSIP family, emphasizes recent advances in elucidating their regulatory roles in tumor-associated signaling pathways, and outlines the major challenges and future perspectives in this emerging field. Full article

Background/Objectives: Chronic constipation is a prevalent gastrointestinal (GI) disorder among individuals with diabetes mellitus (DM), occurring more often than in healthy subjects. This review provides a systematic overview of this often-underestimated clinical condition in people with DM. Methods: A narrative review of literature up to 30 May 2025 was conducted, focusing on studies regarding the pathogenesis of constipation in DM, the correlation with GLP-1 RAs treatment, and the diagnostic-therapeutic framework. Results: The mechanisms underlying constipation in DM remain largely unclear; however, a multifactorial etiology has been proposed, involving structural changes in various tissues within the GI tract wall, as well as functional abnormalities, often secondary to hyperglycemia. It is noteworthy that the use of GLP-1 RAs, a class of medications crucial for managing glycemic control and reducing cardiovascular and renal risk in type 2 DM, is another cause of constipation. The diagnosis of constipation is typically based on clinical evaluation, as validated methods for assessing colonic transit are invasive and available only in specialized centers. Treatment objectives include alleviating symptoms and restoring bowel function. The primary strategy for management involves dietary changes and physical activity. If the clinical response is inadequate, the use of laxatives is recommended. Finally, newer agents and mechanical methods may be considered for scenarios that are particularly severe. Conclusions: Given the increasing global prevalence of DM, healthcare professionals must recognize the clinical problem constituted by the occurrence of chronic constipation, especially considering the use of medications such as GLP-1 RAs that may induce this clinical condition. Full article

Bovine mastitis is one of the most prevalent and economically significant diseases affecting dairy cows worldwide, with Escherichia coli (E. coli) recognized as one of the principal pathogens causing acute mastitis. The innate immune system plays a crucial role in the defense of the bovine mammary gland, serving as the first line of defense against pathogen invasion. This study elucidated the pathological mechanisms and immune response-related molecular regulatory networks involved in E. coli-induced bovine mastitis. Histopathological and apoptosis analyses of mammary tissues were performed using hematoxylin-eosin (HE) staining and TUNEL staining, respectively, while RNA sequencing (RNA-seq) was conducted to identify differentially expressed genes (DEGs) and their associated signaling pathways. HE staining revealed typical inflammatory lesions in the mammary glands of mastitis cows. TUNEL staining further confirmed that the level of apoptosis in the mastitis group was significantly higher than in the healthy control group (p < 0.0001). RNA-seq analysis identified 2717 DEGs, with 2238 upregulated and 479 downregulated genes. The top 20 significantly upregulated genes (e.g., S100A12, IL1RN, IL1R2, CXCL8, SAA3, S100A8, S100A9, TREML2, TREM1, M-SAA3.2, PTX3, MMP9) were predominantly involved in inflammatory immune regulation, acute phase responses (e.g., HP, SAA3), and cellular signal transduction (e.g., PLEK, LPAR3). Gene Ontology (GO) enrichment analysis revealed that these DEGs were mainly associated with biological processes, such as signal transduction, immune response, inflammatory response, and transcriptional regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were significantly enriched in key inflammatory and immune regulatory pathways, including the TNF signaling pathway, C-type lectin receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, NF-κ B signaling pathway, and IL-17 signaling pathway, suggesting that these pathways play central roles in the mammary immune defense against E. coli infection. In conclusion, this study demonstrated at the histopathological, cellular apoptosis, and transcriptomic levels that E. coli infection induces mammary tissue damage and apoptosis by activating immune and inflammation-related genes (S100A12, IL1RN, IL1R2, CXCL8, SAA3, S100A8, S100A9, TREML2, TREM1, M-SAA3.2, PTX3, MMP9) and key signaling pathways (TNF signaling pathway, C-type lectin receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, NF-κ B signaling pathway, IL-17 signaling pathway). The findings of this study provide a theoretical basis for probing into the pathogenesis of bovine mastitis and the development of targeted interventions. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. However, the spatial and temporal dynamics underlying its development remain poorly characterized. This study employs spatial transcriptomics (ST) to investigate the progression of intestinal tumors in APC ^Min/+ mice across multiple time points. We identified distinct transcriptional profiles between tumor and normal tissues, resolving six major cell types through integrated dimensionality reduction and pathological annotation. Pseudo-time trajectory analysis revealed increased expression of MMP11 and MYL9 in later stages of tumor progression. Analysis of human CRC cohorts from the TCGA database further confirmed that high expression of these genes is associated with advanced clinical stages and promotes tumor proliferation and invasion. Temporal gene expression dynamics indicated enrichment of cancer-related pathways concurrent with suppression of lipid and amino acid metabolism. Notably, genes in the DEFA family were significantly upregulated in normal tissues compared to tumor tissues. Functional validation showed that DEFA3 inhibits colon cancer cell migration and proliferation in vitro. These demonstrate the value of ST in resolving spatiotemporal heterogeneity in CRC and identify both MMP11/MYL9 and DEFA3 as potential biomarkers and therapeutic targets. Full article

The recruitment of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) of oral squamous carcinoma (OSCC) affects significant cancer invasion; however, in the normal host tissue that is located in the cancer’s surrounding area, this is poorly investigated. In this study, we examined the impact of gingival connective tissue cells (GCTCs) and periodontal ligament cells (PDLCs), which are involved in the invasive pathway of OSCC, on oral cancer invasion via TAMs recruitment. Transwell (migration) assays were used to examine the effects of GCTCs and PDLCs on the migration of macrophages, which indicated that the interaction between GCTCs and HSC-2/HSC-3 (human oral squamous cell carcinoma cell line) promoted the recruitment of macrophages, whereas the interaction between PDLCs was inhibited. An indirect co-culture was then used to examine the effects of GCTCs and PDLCs on the differentiation of macrophages, which indicated that the interaction between GCTCs enhanced their ability to transform into M2-type macrophages. Furthermore, the effects of GCTCs and PDLCs on the recruitment of CD45(+) monocytes, F4/80(+) M0 macrophages, iNOS(+) M1 macrophages, and CD163(+) M2 TAMs were assayed by immunohistochemistry. The results revealed that the interaction between GCTCs and HSC-2/HSC-3 promoted the infiltration of CD45(+) monocytes, F4/80(+) M0 macrophages, and CD163(+) M2 TAMs, whereas the PDLCs inhibited it, while their effect on iNOS(+) M1 macrophages was limited. Collectively, the GCTCs contributed to the infiltration of TAMs into the TME of OSCC cells, whereas the PDLCs exerted an inhibitory effect. These findings suggest a potential regulatory mechanism underlying the progression of OSCC. Full article

In light of the growing significance of molecular biomarkers in central nervous system tumours, in this study, we aimed to comprehensively and quantitatively analyze the mRNA expression levels of DJ-1 (Parkinsonism-associated deglycase 7, PARK7), GDF15 (Growth Differentiation Factor 15), and MFGE8 (Milk Fat Globule-EGF Factor 8 Protein) in glioma and meningioma tissues and to thoroughly evaluate the associations between these gene expression profiles and clinicopathological parameters. Real-time PCR (qRT-PCR) analyses performed on tumour tissues obtained from a total of 27 glioma and 18 meningioma patients revealed that these three genes exhibited significantly elevated expression compared to control samples. Despite their different cellular origins, statistically significant positive correlations were observed between the expression levels of DJ-1, GDF15, and MFGE8 and both tumour grade and the Ki-67 proliferation index (Ki-67 Pi) in both glioma and meningioma cases, indicating that higher gene expression is associated with increased tumour aggressiveness in both tumour types. Receiver operating characteristic (ROC) curve analyses further confirmed the diagnostic and prognostic potential of these genes. Additionally, protein–protein interaction networks involving the target genes were characterised, providing valuable insights into their molecular mechanisms. These findings suggest that DJ-1, GDF15, and MFGE8 may play a role in the aggressiveness, invasion, and proliferation of gliomas and meningiomas. Moreover, integrating these genes as molecular biomarkers into tumour classification systems may provide a foundation for the development of personalised and targeted therapeutic strategies, although further studies are needed to support this. Full article

Non-coding RNAs (ncRNAs) are critical regulators of gene expression, taking part in the modulation of multiple biological functions across a range of cell types. Initially dismissed as transcriptional noise, ncRNAs are now recognized for their significant roles in key cellular mechanisms, including differentiation, apoptosis, and proliferation, as well as their profound implications for the pathogenesis of numerous human diseases. Due to their remarkable stability, tissue-specific expression patterns, and abundance in body fluids, ncRNAs hold significant promise as non-invasive biomarkers for diagnosis, prognosis, and therapeutic monitoring. Furthermore, advances in RNA-targeted therapeutics have introduced novel strategies to modulate ncRNA activity, although challenges related to delivery efficiency, specificity, and clinical validation remain. This review comprehensively summarizes the classification, biogenesis, and molecular functions of ncRNAs, elucidates their involvement in health and disease, and evaluates their potential as clinical biomarkers and therapeutic targets. Additionally, it discusses the emerging technologies for RNA manipulation, including CRISPR-based RNA editing, that can advance ncRNA research and revolutionize ncRNA-based therapeutics. Full article

Objectives: Cancer is a multifactorial disease determined by several factors. Metabolic disorders such as obesity and diabetes significantly contribute to cancer risk by promoting chronic inflammation, insulin resistance, and hormonal dysregulation. Obesity and hyperglycaemia elevate insulin-like growth factor-1 (IGF-1) levels, driving oncogenic pathways such as PI3K/Akt/mTOR, which promote tumour proliferation and survival. Furthermore, cancer cells undergo metabolic reprogramming, characterised by increased reliance on glycolysis (Warburg effect), facilitating tumour growth and therapy resistance. Hence, body weight reduction and glycaemic control may represent potential strategies for cancer prevention and treatment. Irisin, a myokine secreted by skeletal muscle, plays a critical role in cellular metabolism and energy homeostasis. Emerging evidence suggests that irisin may exert tumour-suppressive effects by modulating key metabolic and oncogenic pathways. Methods: A systematic literature search identified studies investigating irisin’s effects in various cancer models. Results: In vitro, irisin exerts dose- and time-dependent anti-proliferative effects in a variety of cancer cell lines, primarily via PI3K/Akt/mTOR inhibition and AMPK activation, leading to cell cycle arrest and apoptosis. Additionally, irisin inhibits epithelial–mesenchymal transition, which suppresses cancer cell migration and invasion. However, conflicting findings, particularly in hepatocellular carcinoma, suggest tissue-specific responses. Similarly, clinical data regarding systemic and tumoural irisin levels remain inconsistent and appear to vary based on cancer type and stage. Conclusions: Irisin represents a promising therapeutic target due to its ability to modulate metabolic and oncogenic pathways. However, further research is needed to elucidate its clinical relevance and optimise its application as an adjunct to existing cancer therapies. Full article

Background/Objectives: Colorectal cancer (CRC) is the third most common cancer and a leading cause of death worldwide. Identifying non-invasive, early indicators of CRC risk remains essential and could help reduce its health burden. Excess adiposity and chronic inflammation are major predisposing factors for precancerous adenomatous polyposis (AP) and CRC, while diet- or surgery-induced weight loss was associated with a reduced risk. Viral infections also represent cancer risk factors through direct or synergic mechanisms, though no definitive causal link has been established for CRC. Moreover, interest is growing on the role of oral viruses as predictors of disease. Methods: In this study, highly sensitive and specific Luminex-based screening assays were used to perform a comprehensive characterization of oral infections by Human Herpes (HHV), Polyoma (HPyV) and Papilloma (HPV) Viruses in CRC patients (N = 50), healthy controls (N = 46; normal weight, NW = 26; overweight, OW = 20), and high-risk individuals with obesity (N = 35) or adenomatous polyposis (AP, N = 22). Results: We observed increased HPyV prevalence in AP, and higher single and multiple β-HPV infection rates in AP and CRC compared to controls. A panel of β-HPV genotypes, including oncogenic HPV5, was overrepresented in CRC and high-risk groups, and some of them showed an association with the male sex. The prevalence of most infections decreased in the obese cohort following bariatric surgery, alongside weight loss and reduction of inflammatory markers. Furthermore, oral infections by viral types previously detected in CRC tissue and adjacent mucosa also declined after surgery. Conclusions: Altogether, these findings suggested a role for oral β-HPV types as potential sex- and lifestyle-related, modifiable indicators of cancer risk. Full article