Clinical outcomes of endodontic microsurgery in complicated cases with large or through-and-through lesions: a retrospective longitudinal study.

OBJECTIVES: To investigate the clinical outcomes of endodontic microsurgery in complicated cases presenting with large or through-and-through lesions. MATERIALS AND METHODS: We retrospectively collected and analyzed preoperative, intraoperative, and follow-up data from 143 complicated cases that underwent endodontic microsurgery. Clinical outcomes were assessed in terms of tooth survival and surgery success. Cox regression analysis was used to evaluate the survival rate and identify associated risk factors. Additionally, the success rate was compared across different postoperative periods, and potential factors contributing to surgical failure were identified through binary logistic regression. RESULTS: The overall survival and success rates were 93.0% and 91.7%, respectively. The Cox regression model identified four risk factors affecting tooth survival, including apicoectomy of four teeth (HR = 35.488; P = 0.0002), an open apex observed on preoperative radiographs (HR = 6.300; P = 0.025), the performance of guided tissue regeneration technique (HR = 8.846; P = 0.028), and a palatal surgical approach (HR = 8.685; P = 0.030). The success rate demonstrated an initial increase in the early postoperative period (from 0.5 to 2 years; P = 5.8124e-30), followed by stabilization (from 2 to 9 years; P = 0.298). Surgery success rate significantly declined when apicoectomy involved four teeth (OR = 109.412; P = 0.002). CONCLUSIONS: Endodontic microsurgery demonstrates satisfactory outcomes in complicated cases, maintaining a stable success rate after two years. However, tooth survival and surgery success are significantly compromised when apicoectomy involves four teeth. Factors such as guided tissue regeneration, an open apex, and the palatal surgical approach are associated with an increased risk of tooth extraction. CLINICAL RELEVANCE: Despite achieving acceptable outcomes in complicated cases, endodontic microsurgery is adversely affected by the apicoectomy of four teeth.

Limitations and Management of Dynamic Navigation System for Locating Calcified Canals Failure.

Nonsurgical endodontic teeth treatment with severe pulp canal obliteration poses challenges, primarily locating canals. By combining 3-dimensional reconstruction and spatial location registration, the dynamic navigation technique uses an optical tracking system to guide the clinician to drill in real time according to the predesigned path until access to the canal is established. Several in vitro studies and case reports have shown that calcified canal location with dynamic navigation system (DNS) is more accurate and efficient, yet the technique has limitations. In 4 cases with 7 teeth, this work presents manipulation process and clinical outcomes of DNS helping in calcified canal location. We performed handpiece adaptation and elucidated the failure to locate the canals with DNS in 2 teeth, resulting in canal geometry alteration and canal path deviation. Subsequently, the more experienced endodontist located the canals by combining cone-beam computed tomographic imaging and dental operating microscopy. All patients were completely asymptomatic after treatment. At the 1-year follow-up visit, the bone healing of periapical lesions progressed well according to the periapical radiography or cone-beam computed tomographic imaging. These findings indicate that DNS is a promising technique for locating calcified canals; however, it needs to be refined before clinical use.

Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration.

Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.

GelMA-based hydrogel biomaterial scaffold: A versatile platform for regenerative endodontics.

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.

Using metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.

Objective: To accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis. Methods: This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis. Results: The percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group (p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns (p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls. Conclusion: Common variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases.

Serum differential proteomic profiling of patients with isolated methylmalonic acidemia by iTRAQ.

Isolated methylmalonic acidemia (MMA) is an inherited organic acid metabolic disorder in an autosomal recessive manner, caused by mutations in the methylmalonyl coenzyme A mutase gene, and the isolated MMA patients often suffer from multi-organ damage. The present study aimed to profile the differential proteome of serum between isolated MAA patients and healthy control. The in vivo proteome of isolated MAA patients and healthy subjects was detected by an isobaric tag for relative and absolute quantitation (iTRAQ). A total of 94 differentially expressed proteins (DEPs) were identified between MMA patients and healthy control, including 58 upregulated and 36 downregulated DEPs in MMA patients. Among them, the most significantly upregulated proteins were CRP and immunoglobulins, and the top five most significantly downregulated proteins were all different types of immunoglobulins in MMA patients. GO analysis showed that these DEPs were mainly enriched in immune-related function and membrane protein-related function. KEGG revealed that these DEPs were mainly enriched in lysosome and cholesterol metabolism pathways. Also, these DEPs were predicted to contribute to lipid metabolic diseases. We addressed the proteomes of isolated MMA patients and identified DEPs. Our study expands our current understanding of MMA, and the DEPs could be valuable for designing alternative therapies to alleviate MMA symptoms.

The Cortical Network of Emotion Regulation: Insights From Advanced EEG-fMRI Integration Analysis.

The ability to perceive and regulate emotion is a key component of cognition that is often disrupted by disease. Current neuroimaging studies regarding emotion regulation have implicated a number of cortical regions and identified several EEG features of interest, including the late positive potential and frontal asymmetry. Unfortunately, currently applied methods generally lack in the resolution necessary to capture focal cortical activity and explore the causal interactions between brain regions. In this paper, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data were simultaneously recorded from 20 subjects undergoing emotion processing and regulation tasks. Cortical activity with high-spatiotemporal resolution and accuracy was reconstructed using a novel multimodal EEG/fMRI integration method. A detailed causal brain network associated with emotion processing and regulation was then identified, and the network changes that facilitate different emotion conditions were investigated. The cortical activity of the ventrolateral prefrontal (VLPFC) and posterior parietal cortices depicted conditionally-sensitive spike and wave patterns evidenced in inter-regional communication. The VLPFC was found to behave as a main network source, with conditionally-specific interactions supporting emotional shifts. The results provide unique insight into the cortical activity that supports emotional perception and regulation, the origins of known EEG phenomena, and the manner in which brain regions coordinate to affect behavior.

Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer.

We previously observed that the HERV type K (HERV-K) envelope (env) protein was expressed in the majority of human breast tumors from a U.S. cohort of women from Texas. We also made the preliminary observation that the expression of HERV-K env transcripts was associated with markers of disease progression. In this follow-up study, env protein expression was evaluated immunohistochemically in an additional 195 paraffin-embedded breast tumors from a second U.S. patient cohort (Baltimore, Maryland) and in 110 tumors from Chinese patients. Moreover, we compared env transcript expression between fresh-frozen normal and cancerous breast tissues. We observed that while env mRNA and protein expression was undetectable in normal breast tissue and in a subset of uninvolved normal-appearing tissue adjacent to the tumor epithelium, it was overexpressed in most tumors. Furthermore, env expression was associated with breast cancer progression. In Baltimore cohort women, HERV-K tumor positivity was significantly associated with disease stage and lymph node metastasis. In Chinese women, HERV-K env positivity was significantly associated with tumor size, TNM stage, and lymph node metastases, which is consistent with the observations in the U.S. cohort. We also found that Chinese breast cancer patients with a high expression of HERV-K had a decreased overall survival compared with patients who had either a moderate or low HERV-K expression in their tumors (P = 0.049, χ(2) log rank test). In conclusion, the HERV-K env gene is expressed in the majority of breast cancers from U.S. or Chinese women but not in normal breast tissue. High expression of HERV-K env protein in breast cancer patients is associated with markers of disease progression and poor disease outcome, indicating that HERV-K env protein is a novel candidate prognostic marker for breast cancer.

Effect of melatonin and melatonylvalpromide on beta-amyloid and neurofilaments in N2a cells.

In the present study, we have studied the effect of melatonin (Mt) and melatonin derivative, i.e., melatonylvalpromide (Mtv), on cell viability, beta-amyloid (Abeta) production, cell morphology, and expression and phosphorylation of neurofilament proteins in wild-type murine neuroblastoma N2a (N2a/wt) and N2a stably transfected with amyloid precursor protein (N2a/APP) cell lines. The study used MTT assay, Sandwich ELISA, immunocytochemistry and Western blots techniques. The results showed that both Mt and Mtv could increase cell viability, but Mtv did so more effectively. The N2a/APP showed shorter and less amount of cell processes than N2a/wt, and Mtv but not Mt slightly improved the morphological changes in N2A/APP. Both Mt and Mtv suppressed the Abeta level in cell lysates, but the effect of Mtv was stronger than Mt. The immunoreaction to the non-phosphorylated neurofilament proteins probed by SMI32 and SMI33 were remarkably weaker in N2a/APP than N2a/wt, while the immunoreaction to the phosphorylated neurofilament proteins at SMI34 epitopes was slightly stronger in N2a/APP than N2a/wt, suggesting higher phosphorylation level of neurofilament proteins in N2a/APP. Treatment of the cells with Mt and Mtv increased the immunoreaction at SMI32 and SMI33 epitopes, while only Mtv but not Mt decreased the staining at SMI34 epitope, suggesting both Mt and Mtv promote dephosphorylation of neurofilament at SMI32 and SMI33 epitopes, while Mtv stimulates dephosphorylation of neurofilament at SMI34 epitope. These results suggest that Mtv may be a better candidate in arresting the intracellular accumulation of Abeta and protecting the cells from Abeta-related toxicity.