The process of osseointegration for dental implants is complex and can be influenced by localized inflammation. The NF-κB signaling system plays a crucial role in regulating inflammatory responses. This review examines the role of microRNAs (miRNAs) in regulating the NF-κB pathway in inflammatory conditions associated with dental implants, including periodontitis, alveolar bone abnormalities, and estrogen deficiency models. A review of prior research demonstrates that miRNAs, specifically miR-146a, miR-21a-5p, miR-182, and miR-100-5p, modulate NF-κB activation and maintain the balance between osteogenesis and osteoclastogenesis by targeting molecules such as FoxO1, TLR4, and PDCD4. These interactions lead to a reduction in reactive oxygen species, inhibition of pro-inflammatory cytokines (including IL-1β and TNF-α), and an elevation in osteogenic markers (such as Runx2 and ALP). The findings indicate that the miRNA-NF-κB axes can lead to peri-implantitis and implant failure. On the other hand, miRNA-based therapeutics, such as agomirs and antagomirs, might assist in improving osseointegration outcomes. This study highlights the importance of miRNAs in modulating NF-κB inflammation for the effectiveness of dental implants and suggests avenues for further research.
Usually, human life begins with a cry and respiratory distress, and then extends to a diverse set of extrinsic and intrinsic stressors, of which infection, DNA replication stress, and oxidative stress are the most common. These stresses converge to aging and age-related diseases and ultimately toward death, which is the final and profound challenge for human beings. Although immunology has achieved its glory in responding to infectious microorganisms, the roles of the immune system, both in combating various cellular stresses, as well as in generating cellular stress with each heartbeat, are not negligible and need to be further highlighted. Here, we report a summary of more than a decade of our research on serum starvation, replicative cell senescence, and heat shock-mediated cellular stress responses using some advanced laboratory methods and a wide range of preclinical models, suggesting that the threat of cellular stress can be exploited as an opportunity to treat some age-related diseases such as cancer and atherosclerosis. In this brief, the clinical applications of fibroblasts and immune cells' responses to three stressors: serum starvation, replicative cell senescence, and heat shock, are discussed and compared with human ovarian follicular fluid as a control fluid derived from unstressed cell.
A significant mortality is attributed to a common cancer called colorectal cancer (CRC), and current screening methods for CRC could be improved. Circulating microRNAs (miRNAs) have been identified as promising diagnostic biomarkers in body fluids by their rearrangement between healthy and diseased individuals. This study reviewed studies on miRNAs to investigate their use as screening tools for CRC diagnosis. We searched PubMed, Scopus, and Web of Science (WoS) databases to discover and find relevant miRNAs that could be used as diagnostic biomarkers in CRC. Patient number and demographic characteristics, patient sample type, miRNA detection method, normalization type, and significantly dysregulated miRNAs were recorded. Meta-analysis was performed across studies with similar dysregulated miRNAs. Initially, 1207 identified articles were entered into ENDNOTE, of which 422, 393, and 392 were from Scopus, WoS, and PubMed, respectively. After reviewing and screening studies by two researchers separately and removing duplicates and irrelevant ones, 126 articles remained as final articles. In the meta-analysis, 6 distinct miRNAs including miR-21, miR-29, miR-92, miR-135, miR-210, and miR-1290 were identified in 42 studies. To evaluate the diagnostic accuracy of these miRNAs in colorectal cancer, Forest plots were drawn and statistical analysis was performed using the area under the ROC curve (AUC), sensitivity (95% CI), and specificity (95% CI). The results showed that the identified miRNAs discriminated colorectal cancer (CRC) patients from healthy individuals with high sensitivity and specificity and outperformed conventional tumor biomarkers, making miRNAs a potential blood-based marker for colorectal cancer diagnosis.
In systemic lupus erythematosus (SLE), thrombotic events represent a high-risk manifestation associated with autoantibody-induced damage. This underscores the necessity of utilizing biomarkers to assess thrombotic risk and monitor the thrombotic status of patients. D-dimer is a widely used and inexpensive marker routinely-used to assess coagulation disorders. A systematic literature search was conducted from 1990-2024 using the PubMed, Scopus, and Web of Science databases. Included articles reported D-dimer serum levels in both SLE patients and healthy individuals. Data were analyzed using standard mean difference (SMD) with a 95% confidence interval using random effect models. Heterogeneity was assessed based on the Cochran chi-square and I2 statistic. Article quality was assessed via the Newcastle-Ottawa scale. This study incorporated data from 14 studies, encompassing individuals diagnosed with SLE and 1785 healthy participants serving as controls. The results indicated a significant increase in serum D-dimer level in the SLE group compared to the control group (SMD= 0.74, 95% CI 0.49, 1.00, p < 0.001; I2 =87.47%, p < 0.001). Moreover, patients with high SLE disease activity had higher D-dimer levels compared to those with low SLE disease activity (SMD=0.78, 95% CI 0.46, 1.11; I2 =0, p=0.77). Moreover, a significant positive correlation was found between SLE disease activity and D-dimer concentrations (r=0.45, 95% CI 0.34, 0.55, p<0.0001). D-dimer may serve as an indicator of thrombotic status and disease severity in SLE patients. Establishing D-dimer as a reliable biomarker for tracking SLE activity will require well-designed prospective studies that consider standardized assays, control for confounding factors, and incorporate predictive modelling.
Glioblastoma multiform (GBM) is a lethal brain tumor with limited treatment options. This study investigated the combined effect of two natural compounds, formononetin (FMN) and magnolol (MAG), on T98G glioblastoma cells, focusing on oxidative stress mechanisms. Cell viability was assessed via MTT assay to determine IC50 values and synergy (Chou-Talalay method). Proliferation, migration (wound healing), colony formation, and apoptosis (Hoechst staining) were evaluated. Gene expression (qPCR) of targets like survivin, cyclin D1, and antioxidant enzymes (SOD, CAT, GPX) was analyzed. Enzymatic activities and total antioxidant capacity (TAC) were measured. FMN and MAG synergistically reduced cell survival (CI=0.72 at 80 µM each). Combination treatment significantly inhibited proliferation, migration, and colony formation more effectively than single agents. This impounds downregulated pro-survival genes (survivin, cyclin D1, MMP-9) and upregulated pro-apoptotic Bad. Paradoxically, it also enhanced antioxidant enzyme activity and TAC. Despite this compensatory response, the treatment induced significant nuclear fragmentation indicative of apoptosis. The FMN and MAG combination exerts potent synergistic antiglioblastoma effects by disrupting proliferation and survival pathways, ultimately inducing apoptosis, even while triggering a compensatory antioxidant response. These in vitro findings provide a hypothesis-generating foundation for further investigation of formononetin and magnolol as a potential combinatorial approach for glioblastoma, pending rigorous in vivo validation and blood-brain barrier permeability studies.
