Effects of intra-operative magnesium sulfate infusion on orthognathic surgery: A prospective and randomized controlled trial.

Purpose: To comprehensively understand the effects of intra-operative infusion of magnesium sulfate on patients who underwent orthognathic surgery, including remifentanil consumption, postoperative pain, postoperative nausea and vomiting (PONV), inflammatory response, and serum magnesium levels. Methods: Seventy-five adult patients undergoing orthognathic surgery under general balanced anesthesia were randomly divided into two groups. One group (Group M) received 50 mg/kg of magnesium sulfate in 20 mL 0.9 % saline after intubation, followed by a continuous infusion at a rate of 15 mg/kg/h until 30 min before the anticipated end of surgery. The other group (Group C) received an equal volume of isotonic saline as a placebo. (Clinical trial registration number: chiCTR2100045981). Results: The primary outcome was remifentanil consumption. The secondary outcomes included the pain score assessed using the verbal numerical rating scale (VNRS) and PONV assessed using a Likert scale. Remifentanil comsumption in Group M was lower than Group C (mean ± SD: 0.146 ± 0.04 µg/kg/min vs. 0.173 ± 0.04 µg/kg/min, P = 0.003). At 2 h after surgery, patients in Group C suffered more severe PONV than those in Group M (median [interquartile range, IQR]: 1 [3] vs. 1 [0], mean rank: 31.45 vs. 42.71, P = 0.040). At post-anesthesia care unit (PACU), postoperative pain in Group C was severe than Group M (3 [1] vs. 3 [0], mean rank: 31.45 vs. 42.71, P = 0.013). Changes in haemodynamics and surgical field scores did not differ between the groups (all P > 0.05). The levels of cytokines (IL-4, IL-6, IL-8, IL-10, TNF-a, and MIP-1ß) were not significantly different between the groups after surgery (all P > 0.05). Postoperative serum magnesium levels in Group C were lower than those in Group M (0.74 ± 0.07 mmol/L vs. 0.91 ± 0.08 mmol/L, P = 0.000) and the preoperative level (0.74 ± 0.07 mmol/L vs. 0.83 ± 0.06 mmol/L, P = 0.219). Conclusions: In orthognathic surgery, magnesium sulfate administration can reduce remifentanil requirement and relieve PONV and postoperative pain in the early postoperative phase.

Systemic inflammation, neuroinflammation and perioperative neurocognitive disorders.

Perioperative neurocognitive disorder (PND) is a common disorder following anesthesia and surgery, especially in the elderly. The complex cellular and molecular processes are involved in PND, but the underlying pathogenesis of which remains inconclusive due to conflicting data. A growing body of evidence has been shown that perioperative systemic inflammation plays important roles in the development of PND. We reviewed the relevant literature retrieved by a search in the PubMed database (on July 20, 2023). The search terms used were "delirium", "post operative cognitive dysfunction", "perioperative neurocognitive disorder", "inflammation" and "systemic", alone and in combination. All articles identified were English-language, full-text papers. The ones cited in the review are those that make a substantial contribution to the knowledge about systemic inflammation and PNDs. The aim of this review is to bring together the latest evidence for the understanding of how perioperative systemic inflammation mediates neuroinflammation and brain injury, how the inflammation is regulated and how we can translate these findings into prevention and/or treatment for PND.

Promotive Effect of FBXO32 on the Odontoblastic Differentiation of Human Dental Pulp Stem Cells.

Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) is crucial for the intricate formation and repair processes in dental pulp. Until now, the literature is not able to demonstrate the role of ubiquitination in the odontoblastic differentiation of hDPSCs. This study investigated the role of F-box-only protein 32 (FBXO32), an E3 ligase, in the odontoblastic differentiation of hDPSCs. The mRNA expression profile was obtained from ribonucleic acid sequencing (RNA-Seq) data and analyzed. Immunofluorescence and immunohistochemical staining identify the FBXO32 expression in human dental pulp and hDPSCs. Small-hairpin RNA lentivirus was used for FBXO32 knockdown and overexpression. Odontoblastic differentiation of hDPSCs was determined via alkaline phosphatase activity, Alizarin Red S staining, and mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction and Western blotting. Furthermore, subcutaneous transplantation in nude mice was performed to evaluate the role of FBXO32 in mineralization in vivo using histological analysis. FBXO32 expression was upregulated in the odontoblast differentiated hDPSCs as evidenced by RNA-Seq data analysis. FBXO32 was detected in hDPSCs and the odontoblast layer of the dental pulp. Increased FBXO32 expression in hDPSCs during odontoblastic differentiation was confirmed. Through lentivirus infection method, FBXO32 downregulation in hDPSCs attenuated odontoblastic differentiation in vitro and in vivo, whereas FBXO32 upregulation promoted the hDPSCs odontoblastic differentiation, without affecting proliferation and migration. This study demonstrated, for the first time, the promotive role of FBXO32 in regulating the odontoblastic differentiation of hDPSCs, thereby providing novel insights into the regulatory mechanisms during odontoblastic differentiation in hDPSCs.

Melatonin promoted osteogenesis of human periodontal ligament cells by regulating mitochondrial functions through the translocase of the outer mitochondrial membrane 20.

BACKGROUND AND OBJECTIVE: Melatonin plays an important role in various beneficial functions, including promoting differentiation. However, effects on osteogenic differentiation, especially in human periodontal cells (hPDLCs), still remain inconclusive. Mitochondria are highly dynamic organelles that play an important role in various biological processes in cells, including energy metabolism and oxidative stress reaction. Furthermore, the translocase of the outer mitochondrial membrane 20 (TOM20) is responsible for recognizing and transporting precursor proteins. Thus, the objective of this study was to evaluate the functionality of melatonin on osteogenesis in human periodontal cells and to explore the involved mechanism of mitochondria. METHODS: The hPDLCs were extracted and identified by flow cytometry and multilineage differentiation. We divided hPDLCs into control group, osteogenic induction group, and osteogenesis with melatonin treatment group (100, 10, and 1 µM). Then we used a specific siRNA to achieve interference of TOM20. Alizarin red and Alkaline phosphatase staining and activity assays were performed to evaluate osteogenic differentiation. Osteogenesis-related genes and proteins were measured by qPCR and western blot. Mitochondrial functions were tested using ATP, NAD+/NADH, JC-1, and Seahorse Mito Stress Test kits. Finally, TOM20 and mitochondrial dynamics-related molecules expression were also assessed by qPCR and western blot. RESULTS: Our results showed that melatonin-treated hPDLCs had higher calcification and ALP activity as well as upregulated OCN and Runx2 expression at mRNA and protein levels, which was the most obvious in 1 µM melatonin-treated group. Meanwhile, melatonin supplement elevated intracellular ATP production and mitochondrial membrane potential by increasing mitochondrial oxidative metabolism, hence causing a lower NAD+ /NADH ratio. In addition, we also found that melatonin treatment raised TOM20 level and osteogenesis and mitochondrial functions were both suppressed after knocking down TOM20. CONCLUSION: We found that melatonin promoted osteogenesis of hPDLCs and 1 µM melatonin had the most remarkable effect. Melatonin treatment can reinforce mitochondrial functions by upregulating TOM20.

Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight.

Recent studies have indicated a central role for LonP1 in mitochondrial function. Its physiological functions include proteolysis, acting as a molecular chaperone, binding mitochondrial DNA, and being involved in cellular respiration, cellular metabolism, and oxidative stress. Given its vital role in energy metabolism, LonP1 has been suggested to be associated with multi-system neoplasms and developmental disorders. In this study, we investigated the roles, possible mechanisms of action, and therapeutic roles of LonP1 in oral and maxillofacial tumor development. LonP1 was highly expressed in oral-maxillofacial cancers and regulated their development through a sig-naling network. LonP1 may therefore be a promising anticancer therapy target. Mutations in LONP1 have been found to be involved in the etiology of cerebral, ocular, dental, auricular, and skeletal syndrome (CODAS). Only patients carrying specific LONP1 mutations have certain dental abnormalities (delayed eruption and abnormal morphology). LonP1 is therefore a novel factor in the development of oral and maxillofacial tumors. Greater research should therefore be conducted on the diagnosis and therapy of LonP1-related diseases to further define LonP1-associated oral phenotypes and their underlying molecular mechanisms.

Single-cell RNA sequencing reveals distinct transcriptional features of the purinergic signaling in mouse trigeminal ganglion.

Trigeminal ganglion (TG) is the first station of sensory pathways in the orofacial region. The TG neurons communicate with satellite glial cells (SGCs), macrophages and other cells forming a functional unit that is responsible for processing of orofacial sensory information. Purinergic signaling, one of the most widespread autocrine and paracrine pathways, plays a crucial role in intercellular communication. The multidirectional action of purinergic signaling in different cell types contributes to the neuromodulation and orofacial sensation. To fully understand the purinergic signaling in these processes, it is essential to determine the shared and unique expression patterns of genes associated with purinergic signaling in different cell types. Here, we performed single-cell RNA sequencing of 22,969 cells isolated from normal mouse TGs. We identified 18 distinct cell populations, including 6 neuron subpopulations, 3 glial subpopulations, 7 immune cell subpopulations, fibroblasts, and endothelial cells. We also revealed the transcriptional features of genes associated with purinergic signaling, including purinergic receptors, extracellular adenosine triphosphate (eATP) release channels, eATP metabolism-associated enzymes, and eATP transporters in each cell type. Our results have important implications for understanding and predicting the cell type-specific roles of the purinergic signaling in orofacial signal processing in the trigeminal primary sensory system.

Brilliant glycans and glycosylation: Seq and ye shall find.

Proteoglycosylation is the addition of monosaccharides or glycans to the protein peptide chain. This is a common post-translational modification of proteins with a variety of biological functions. At present, more than half of all biopharmaceuticals in clinic are modified by glycosylation. Most glycoproteins are potential drug targets and biomarkers for disease diagnosis. Therefore, in-depth study of glycan structure of glycoproteins will ultimately improve the sensitivity and specificity of glycoproteins for clinical disease detection. With the deepening of research, the function and application value of glycans and glycosylation has gradually emerged. This review systematically introduces the latest research progress of glycans and glycosylation. It encompasses six cancers, four viruses, and their latest discoveries in Alzheimer's disease, allergic diseases, congenital diseases, gastrointestinal diseases, inflammation, and aging.

Principles of RNA methylation and their implications for biology and medicine.

RNA methylation is a post-transcriptional level of regulation. At present, more than 150 kinds of RNA modifications have been identified. They are widely distributed in messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), noncoding small RNA (sncRNA) and long-chain non-coding RNA (lncRNA). In recent years, with the discovery of RNA methylation related proteins and the development of high-throughput sequencing technology, the mystery of RNA methylation has been gradually revealed, and its biological function and application value have gradually emerged. In this review, a large number of research results of RNA methylation in recent years are collected. Through systematic summary and refinement, this review introduced RNA methylation modification-related proteins and RNA methylation sequencing technologies, as well as the biological functions of RNA methylation, expressions and applications of RNA methylation-related genes in physiological or pathological states such as cancer, immunity and virus infection, and discussed the potential therapeutic strategies.

The Role of Microglia in Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorder (PND) is a common phenomenon associated with anesthesia and surgery and has been frequently described in the elderly and susceptible individuals. Microglia, which are the brain's major resident immune cells, play critical roles in maintaining neuronal homeostasis and synaptic plasticity. Accumulating evidence suggests microglial dysfunction occurring after anesthesia and surgery might perturb neuronal function and induce PND. This review aims to provide an overview of the involvement of microglia in PND to date. Possible cellular and molecular mechanisms regarding the connection between microglial activation and PND are discussed.

The emerging roles of artificial intelligence in cancer drug development and precision therapy.

Artificial intelligence (AI) has strong logical reasoning ability and independent learning ability, which can simulate the thinking process of the human brain. AI technologies such as machine learning can profoundly optimize the existing mode of anticancer drug research. But at present AI also has its relative limitation. In this paper, the development of artificial intelligence technology such as deep learning and machine learning in anticancer drug research is reviewed. At the same time, we look forward to the future of AI.

Role of Melatonin in the Regulation of Pain.

Melatonin is a pleiotropic hormone synthesized and secreted mainly by the pineal gland in vertebrates. Melatonin is an endogenous regulator of circadian and seasonal rhythms. Melatonin is involved in many physiological and pathophysiological processes demonstrating antioxidant, antineoplastic, anti-inflammatory, and immunomodulatory properties. Accumulating evidence has revealed that melatonin plays an important role in pain modulation through multiple mechanisms. In this review, we examine recent evidence for melatonin on pain regulation in various animal models and patients with pain syndromes, and the potential cellular mechanisms.

Effects of Targeted Delivery of Metformin and Dental Pulp Stem Cells on Osteogenesis via Demineralized Dentin Matrix under High Glucose Conditions.

High glucose condition inhibited osteoblast differentiation could be a main mechanism contributing to the decreased bone repair associated with diabetes. Metformin, a widely prescribed antidiabetic drug, was shown to have osteogenic properties in our previous study. Transplanted mesenchymal stromal cells (MSCs) may differentiate into osteoblasts and promote bone regeneration. Our study aimed to combine the benefits of metformin and MSCs transplantation on osteogenesis in high glucose conditions. We developed demineralized dentin matrix (DDM) as a carrier to target deliver metformin and dental pulp-derived MSCs (DPSCs). We collected clinically discarded teeth, isolated DPSCs from the dental pulp, and prepared the DDM from the dentin. The DDM was observed by scanning electron microscopy and was found to have well-distributed tubes. Then, metformin was loaded into the DDM to form the DDM-Met complex (DDM-Met); DDM-Met released metformin at a favorable concentration. The DPSCs seeded with the DDM-Met in a high glucose medium showed satisfactory attachment and viability together with increased mineralization and upregulated osteogenesis-related genes, including alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (Runx2), and osteopontin (OPN). A possible mechanism of the enhanced osteogenic differentiation of DPSCs was explored, and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway was found to play a role in the enhancement of osteogenesis. DDM-Met appeared to be a successful metformin and DPSC carrier that allowed for the local delivery of metformin and DPSCs in high glucose conditions. DDM-Met-DPSC construct has promising prospects to promote osteogenesis and enhance the much-needed diabetic bone regeneration.

Oral microbiota and gastrointestinal cancer.

The microbiota inhabiting the oral cavity is a complex ecosystem and responsible for resisting pathogens, maintaining homeostasis, and modulating the immune system. Some components of the oral microbiota contribute to the etiology of some oral diseases. Accumulating evidence suggests that the human oral microbiota is implicated in the development and progression of gastrointestinal cancer. In this review, we described the current understanding of possible roles and mechanisms of oral microbiota in the gastrointestinal cancers studied to date. The perspectives for oral microbiota as the biomarkers for early detection and new therapeutic targets were also discussed.

Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy.

Stem cells are biological cells that can self-renew and can differentiate into multiple cell lineages. Stem cell-based therapy is emerging as a promising alternative therapeutic option for various disorders. Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are isolated from various tissues and can be used as an alternative to embryonic stem cells. Stem cells from the apical papilla (SCAPs) are a novel population of MSCs residing in the apical papilla of immature permanent teeth. SCAPs present the characteristics of expression of MSCs markers, self-renewal, proliferation, migration, differentiation, and immunosuppression, which support the application of SCAPs in stem cell-based therapy, including the immunotherapy and the regeneration of dental tissues, bone, neural, and vascular tissues. In view of these properties and therapeutic potential, SCAPs can be considered as promising candidates for stem cell-based therapy. Thus the aim of our review was to summarize the current knowledge of SCAPs considering isolation, characterization, and multilineage differentiation. The prospects for their use in stem cell-based therapy were also discussed.

A rare CHD5 haplotype and its interactions with environmental factors predicting hepatocellular carcinoma risk.

BACKGROUND: CHD5 is a conventional tumour-suppressing gene in many tumours. The aim of this study was to determine whether CHD5 variants contribute to the risk of hepatocellular carcinoma (HCC). METHODS: Gene variants were identified using next-generation sequencing targeted on referenced mutations followed by TaqMan genotyping in two case-control studies. RESULTS: We discovered a rare variant (haplotype AG) in CHD5 (rs12564469-rs9434711) that was markedly associated with the risk of HCC in a Chinese population. A logistical regression model and permutation test confirmed the association. Indeed, the association quality increased in a gene dose-dependent manner as the number of samples increased. In the stratified analysis, this haplotype risk effect was statistically significant in a subgroup of alcohol drinkers. The false-positive report probability and multifactor dimensionality reduction further supported the finding. CONCLUSIONS: Our results suggest that the rare CHD5 gene haplotype and alcohol intake contribute to the risk of HCC. Our findings can be valuable to researchers of cancer precision medicine looking to improve diagnosis and treatment of HCC.

The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma.

Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions.

Changes of mitochondrial respiratory function during odontogenic differentiation of rat dental papilla cells.

Dental papilla cells (DPCs) belong to precursor cells differentiating to odontoblasts and play an important role in dentin formation and reproduction. This study aimed to explore the changes and and involvement of mitochondrial respiratory function during odontogenic differentiation. Primary DPCs were obtained from first molar dental papilla of neonatal rats and cultured in odontogenic medium for 7, 14, 21 days. DPCs, which expressed mesenchymal surface markers CD29, CD44 and CD90, had the capacity for self-renewal and multipotent differentiation. Odontoblastic induction increased mineralized matrix formation in a time-dependent manner, which was accompanied by elevated alkaline phosphatase (ALP), dentin sialophosphoprotein and dentin matrix protein 1 expression at mRNA and protein levels. Notably, odontogenic medium led to an increase in adenosine-5'-triphosphate content and mitochondrial membrane potential, whereas a decrease in intercellular reactive oxygen species production and NAD+/NADH ratio. Furthermore, odontogenic differentiation was significantly suppressed by treatment with rotenone, an inhibitor of mitochondrial respiratory chain. These results demonstrate that enhanced mitochondrial function is crucial for odontogenic differentiation of DPCs.

Effects of melatonin on the proliferation and differentiation of human dental pulp cells.

OBJECTIVE: Effects of melatonin on the proliferation and differentiation of human dental pulp cells (hDPCs) remain unclear. The purpose of this study was to investigate the effect of melatonin on the proliferation and differentiation of the hDPCs. DESIGN: Primary hDPCs were obtained from the third molar of volunteer aged from 18 to 25. CCK8 assay evaluated the effect of melatonin upon cell proliferation at day 1, 2, 3, 4, 5. After 7days' osteogenic induction with melatonin or vehicle, alkaline phosphatase (ALP) activity was measured with a commercial kit. Then levels of dentin sialophosphoprotein (DSPP) were determined by immunocytochemical staining and western blot analysis, followed by quantitative real-time reverse transcription-Polymerase chain reaction (qRT-PCR) to analyse mRNA levels of ALP and DSPP. Finally hDPCs exposed to osteogenic medium containing melatonin or vehicle for 14days were stained with alizarin red to detect mineralization nodules formation. RESULTS: Melatonin significantly inhibited the proliferative ability of the hDPCs in a concentration- and time-dependent manner. The hDPCs cultured in osteogenic induction medium with melatonin presented an increase of ALP activity, expression of DSPP, mRNA levels of ALP and DSPP, and mineralization nodules formation. CONCLUSIONS: These findings indicate that melatonin at physiological concentrations can inhibit proliferation and promote the differentiation of hDPCs, which might give some new insights into the mechanism of regulating DPCs to achieve dentine regeneration.

Niche astrocytes promote the survival, proliferation and neuronal differentiation of co-transplanted neural stem cells following ischemic stroke in rats.

Niche astrocytes have been reported to promote neuronal differentiation through juxtacrine signaling. However, the effects of astrocytes on neuronal differentiation following ischemic stroke are not fully understood. In the present study, transplanted astrocytes and neural stem cells (NSCs) were transplanted into the ischemic striatum of transient middle cerebral artery occlusion (MCAO) model rats 48 h following surgery. It was observed that the co-transplantation of astrocytes and NSCs resulted in a higher ratio of survival and proliferation of the transplanted NSCs, and neuronal differentiation, in MCAO rats compared with NSC transplantation alone. These results demonstrate that the co-administration of astrocytes promotes the survival and neuronal differentiation of NSCs in the ischemic brain. These results suggest that the co-transplantation of astrocytes and NSCs is more effective than NSCs alone in the production of neurons following ischemic stroke in rats.

9q33.3, a stress-related chromosome region, contributes to reducing lung squamous cell carcinoma risk.

BACKGROUND: Human chromosome 9q33.3 is one of the most important loci for pathophysiological stresses with complex genetic traits. We hypothesized that the common single-nucleotide polymorphisms on this region may affect non-small-cell lung cancer risk. METHODS: We genotyped 43 single-nucleotide polymorphisms that span 13 genes on 9q33.3 in two independent cohorts: the discovery study including 485 cases and 532 controls (North China) and the replicative study including 1063 cases and 1247 controls (South China). Both of the discovery cohort and the replicative cohort were included in the combined study. RESULTS: In the discovery study, we identified a potential protective locus rs10118570 in mitogen-activated protein kinase associated protein 1 with a lower population attributable risk under logistical regression adjusted by age, gender, smoking, and drinking status (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI] 0.10-0.71, p = 1.138 × 10 for genotype GG in lung squamous cell carcinoma). This protective quality increased in a dose-dependent manner as genotype GG decreased (ptrend = 9.675 × 10). Replicative and combined studies showed consistent association for this genotype (replicative: adjusted OR 0.36, 95% CI 0.20-0.66, p = 6.109 × 10, ptrend = 7.386 × 10; combined: adjusted OR 0.33, 95% CI 0.18-0.55, p = 1.259 × 10, ptrend = 7.725 × 10). CONCLUSION: We concluded that mitogen-activated protein kinase associated protein 1 rs10118570 may be an important protective factor for developing better management strategies in lung squamous cell carcinoma.