The Global Prevalence of Middle Mesial Canal in Mandibular First and Second Molars Assessed by Cone Beam Computed Tomography: A Systematic Review and Meta-Analysis.

INTRODUCTION: This meta-analysis sought to identify the in vivo prevalence and influencing factors of middle mesial canal (MMC) in mandibular first and second molars based on cone-beam computed tomography (CBCT) scans. METHODS: MEDLINE/PubMed, Web of Science, Scopus, SciELO, Google Scholar databases/search engines were searched in period between 15th and 21st November 2022, to retrieve the in vivo CBCT-based studies that assessed the prevalence of MMC in mandibular first and/or second molars. The studies were strictly assessed using predefined inclusion and exclusion criteria for relevancy and eligibility through screening the title and abstract, and then assessed through reading the full texts using the same criteria. Subsequently, the fulfilled studies were assessed qualitatively using the Newcastle-Ottawa Quality Assessment Scale, and quantitatively using meta-analysis to calculate the pooled prevalence rates of MMC. The publication bias was assessed using funnel plot and Egger's test. RESULTS: Out of 1122 studies, 33 studies comprised of 13,349 and 7624 mandibular first and second molars, respectively, were eligible for inclusion. Twenty studies scored high quality, while 13 scored moderate quality. The global prevalence of MMC in the first molar was 4.4% (95% CI = 0.035-0.053, P < .001), significantly higher than that of the second molar which was 1.3% (95%, CI = 0.008-0.018, P < .001). Gender, molar side, and age were not influencing factors of MMC prevalence. CONCLUSIONS: The prevalence of MMC is not uncommon, being higher in the mandibular first molar compared to the mandibular second molar. The prevalence of MMC is not influenced by age, molar's side, and gender.

Exploring the neurogenic differentiation of human dental pulp stem cells.

Human dental pulp stem cells (hDPSCs) have increasingly gained interest as a potential therapy for nerve regeneration in medicine and dentistry, however their neurogenic potential remains a matter of debate. This study aimed to characterize hDPSC neuronal differentiation in comparison with the human SH-SY5Y neuronal stem cell differentiation model. Both hDPSCs and SH-SY5Y could be differentiated to generate typical neuronal-like cells following sequential treatment with all-trans retinoic acid (ATRA) and brain-derived neurotrophic factor (BDNF), as evidenced by significant expression of neuronal proteins ßIII-tubulin (TUBB3) and neurofilament medium (NF-M). Both cell types also expressed multiple neural gene markers including growth-associated protein 43 (GAP43), enolase 2/neuron-specific enolase (ENO2/NSE), synapsin I (SYN1), nestin (NES), and peripherin (PRPH), and exhibited measurable voltage-activated Na+ and K+ currents. In hDPSCs, upregulation of acetylcholinesterase (ACHE), choline O-acetyltransferase (CHAT), sodium channel alpha subunit 9 (SCN9A), POU class 4 homeobox 1 (POU4F1/BRN3A) along with a downregulation of motor neuron and pancreas homeobox 1 (MNX1) indicated that differentiation was more guided toward a cholinergic sensory neuronal lineage. Furthermore, the Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 significantly impaired hDPSC neuronal differentiation and was associated with reduction of the ERK1/2 phosphorylation. In conclusion, this study demonstrates that extracellular signal-regulated kinase/Mitogen-activated protein kinase (ERK/MAPK) is necessary for sensory cholinergic neuronal differentiation of hDPSCs. hDPSC-derived cholinergic sensory neuronal-like cells represent a novel model and potential source for neuronal regeneration therapies.