Role of epigenetic regulatory mechanisms in age-related bone homeostasis imbalance.

Alterations to the human organism that are brought about by aging are comprehensive and detrimental. Of these, an imbalance in bone homeostasis is a major outward manifestation of aging. In older adults, the decreased osteogenic activity of bone marrow mesenchymal stem cells and the inhibition of bone marrow mesenchymal stem cell differentiation lead to decreased bone mass, increased risk of fracture, and impaired bone injury healing. In the past decades, numerous studies have reported the epigenetic alterations that occur during aging, such as decreased core histones, altered DNA methylation patterns, and abnormalities in noncoding RNAs, which ultimately lead to genomic abnormalities and affect the expression of downstream signaling osteoporosis treatment and promoter of fracture healing in older adults. The current review summarizes the impact of epigenetic regulation mechanisms on age-related bone homeostasis imbalance.

Full life cycle changes of low impacted mandibular third molar associated cystic lesions and adjacent tooth root resorption: a retrospective study.

OBJECTIVE: Low impacted third molars are usually asymptomatic and are often found by X-ray examination. The removal of asymptomatic low impacted third molars is one of the most controversial clinical issues in oral and maxillofacial surgery. METHODS: In this study, 806 patients with low impacted mandibular third molars (LIMTMs) (full bony impaction) were analyzed to determine the prevalence and risk factors for cystic lesions and adjacent tooth root resorption throughout the patients' entire life cycle. RESULTS: The results showed that the prevalence of adjacent tooth root resorption and cystic lesions was age-related, exhibiting a trend of first increasing and then decreasing; prevalence peaked at the age of 41 to 45 years old, the prevalence rates were 12.50% and 11.11% respectively. And the lowest prevalence rate was 2.86% and 2.44% in ≥ 61 group and 56- to 60-year age group respectively. Age was an independent risk factor for adjacent tooth root resorption of LIMTMs, whereas age and impaction type (especially inverted impaction) were independent risk factors for cystic lesions. CONCLUSIONS: The full life cycle management strategy for LIMTMs may need to be individualized. Surgical removal is recommended for LIMTMs in patients younger than 41 to 45 years, especially for inverted, mesioangular, and horizontally impacted LIMTMs. LIMTMs in patients older than 41 to 45 years may be treated conservatively with regular follow-up, but surgical removal of inverted impacted LIMTMs is still recommended to avoid cyst formation.

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Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.

Efficient Removal of Dental Plaque Biofilm from Training Typodont Teeth via Water Flosser.

Plaque biofilms play critical roles in the development of dental caries. Mechanical plaque control methods are considered to be most effective for plaque removal, such as brushing teeth or using flosser. Recently, water flosser has been paid much attention. Here, we tested the ability of a water flosser to remove the adhered sucrose and the dental plaque biofilms formed by Streptococcus mutans, Streptococcus sanguinis, and Actinobacillus viscosus. We found that the residual sucrose concentration was 3.54 mg/mL in the control group, 1.75 mg/mL in the syringe group (simulating the ordinary mouthwash), and 0 mg/mL in water flosser group. In addition, the residual bacterial concentration was 3.6 × 108 CFU/mL in the control group, 1.6 × 107 CFU/mL in the syringe group, and only 5.5 × 105 CFU/mL in the water flosser group. In summary, water flosser is effective for cleaning the teeth, which may have significant potential in preventing dental caries and maintaining oral health.

Prevention of bacterial biofilm formation on orthodontic brackets by non-crosslinked chitosan coating.

During orthodontic treatment, the patients are susceptible to dental caries as a result of the bacterial adhesion and biofilm formation around the orthodontic brackets. Prevention of the caries-related biofilm formation is of significance for maintaining both aesthetics and health of the teeth. Herein, the brackets were functionalized with antibacterial activity via coating a layer of non-crosslinked chitosan (CS). We firstly demonstrated the ability of free CS scaffolds (not coated on brackets) to inhibit the formation of Streptococcus mutans biofilms (inhibition rate 94.3 % for CS-0.3 mg) and to eradicate the mature biofilms (biofilm loss rate 99.8 % for CS-1.2 mg). Further, the inhibition of S. mutans biofilm formation on brackets by CS coating was investigated for the first time. As a result, the CS-coated brackets (Br-CS) kept the great biofilm inhibition capacity of free CS scaffolds. In detail, the Br-CS, prepared by immersing brackets in CS solutions (containing 1.0, 2.5, 5.0 and 10 mg/mL CS) and freeze-drying, showed the biofilm inhibition rate of 48.5 %, 88.6 %, 96.4 % and 99.6 %, respectively. In conclusion, coating orthodontic brackets with the non-crosslinked CS is a potential approach for inhibiting biofilm formation and protecting patients from dental caries.

The role of PERK-eIF2α-ATF4-CHOP pathway in sevoflurane induced neuroapoptosis and cognitive dysfunction in aged mice.

Postoperative cognitive dysfunction (POCD) is a common surgical complication that causes additional pain in patients and affects their quality of life. To address this problem, emerging studies have focused on the POCD. Recent studies have shown that aging and anesthetic exposure are the two major risk factors for developing POCD. However, few reports described the exact molecular mechanisms underlying POCD in elderly patients. In the previous studies, the endoplasmic reticulum (ER) stress and neuroapoptosis in the hippocampus were associated with inducing POCD; however, no further information on the related signaling pathways could be disclosed. The PERK-eIF2α-ATF4-CHOP pathway is identified as the main regulatory pathway involved in ER stress and cell apoptosis. Therefore, we assume that the occurrence of POCD induced by sevoflurane inhalation may potentially result from ER stress and neuroapoptosis in the hippocampus of aged mice mediated by the PERK-eIF2α-ATF4-CHOP pathway. In our study, we found a relationship between sevoflurane inhalation concentration and memory decline in aged mice, with a 'ceiling effect'. We have confirmed that POCD induced by sevoflurane results from ER stress and neuroapoptosis in the hippocampus of aged mice, which is regulated by the over-expression of PERK-eIF2α-ATF4-CHOP pathway. Furthermore, we also showed that the dephosphorylation inhibitor of eIF2α (salubrinal) could down-regulate PERK-eIF2α-ATF4-CHOP pathway expression to inhibit ER stress and enhance the cognitive function of aged mice. In general, our study has elucidated one of the molecular mechanisms of sevoflurane-related cognitive dysfunction in aged groups and provided new strategies for treating sevoflurane-induced POCD.

Curcumin and analogues against head and neck cancer: From drug delivery to molecular mechanisms.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most life-threatening diseases which also causes economic burden worldwide. To overcome the limitations of traditional therapies, investigation into alternative adjuvant treatments is crucial. PURPOSE: Curcumin, a turmeric-derived compound, demonstrates significant therapeutic potential in diverse diseases, including cancer. Furthermore, research focuses on curcumin analogues and novel drug delivery systems, offering approaches for improved efficacy. This review aims to provide a comprehensive overview of curcumin's current findings, emphasizing its mechanisms of anti-HNSCC effects and potential for clinical application. METHOD: An electronic search of Web of Science, MEDLINE, and Embase was conducted to identify literature about the application of curcumin or analogues in HNSCC. Titles and abstracts were screened to identify potentially eligible studies. Full-text articles will be obtained and independently evaluated by two authors to make the decision of inclusion in the review. RESULTS: Curcumin's clinical application is hindered by poor bioavailability, prompting the exploration of methods to enhance it, such as curcumin analogues and novel drug delivery systems. Curcumin could exhibit anti-cancer effects by targeting cancer cells and modulating the tumor microenvironment in HNSCC. Mechanisms of action include cell cycle arrest, apoptosis promotion, reactive oxygen species induction, endoplasmic reticulum stress, inhibition of epithelial-mesenchymal transition, attenuation of extracellular matrix degradation, and modulation of tumor metabolism in HNSCC cells. Curcumin also targets various components of the tumor microenvironment, including cancer-associated fibroblasts, innate and adaptive immunity, and lymphovascular niches. Furthermore, curcumin enhances the anti-cancer effects of other drugs as adjunctive therapy. Two clinical trials report its potential clinical applications in treating HNSCC. CONCLUSION: Curcumin has demonstrated therapeutic potential in HNSCC through in vitro and in vivo studies. Its effectiveness is attributed to its ability to modulate cancer cells and interact with the intricate tumor microenvironment. The development of curcumin analogues and novel drug delivery systems has shown promise in improving its bioavailability, thereby expanding its clinical applications. Further research and exploration in this area hold great potential for harnessing the full therapeutic benefits of curcumin in HNSCC treatment.

Physiology of pregnancy and oral local anesthesia considerations.

Background: Safe and effective local anesthesia is a prerequisite for emergency oral surgeries and most dental treatments. Pregnancy is characterized by complex physiological changes, and increased sensitivity to pain. Pregnant women are particularly vulnerable to oral diseases, such as caries, gingivitis, pyogenic granuloma and third molar pericoronitis. Maternally administered drugs can affect the fetus through the placenta. Therefore, many physicians and patients are reluctant to provide or accept necessary local anesthesia, which leads to delays in the condition and adverse consequences. This review is intended to comprehensively discuss the instructions for local anesthesia in the oral treatment of pregnant patients. Methodology: An in-depth search on Medline, Embase, and the Cochrane Library was performed to review articles concerned with maternal and fetal physiology, local anesthetic pharmacology, and their applications for oral treatment. Results: Standard oral local anesthesia is safe throughout the pregnancy. At present, 2% lidocaine with 1:200,000 epinephrine is considered to be the anesthetic agent that best balances safety and efficacy for pregnant women. Maternal and fetal considerations must be taken into account to accommodate the physiological and pharmacological changes in the gestation period. Semi-supine position, blood pressure monitoring, and reassurance are suggested for high-risk mothers to reduce the risk of transient changes in blood pressure, hypoxemia, and hypoglycemia. For patients with underlying diseases, such as eclampsia, hypertension, hypotension, and gestational diabetes, the physicians should use epinephrine cautiously and control the dose of anesthetic. New local anesthesia formulations and equipment, which contribute to minimizing injection pain and relieving the anxiety, have and are being developed but remain understudied. Conclusions: Understanding the physiological and pharmacological changes during pregnancy is essential to ensure the safety and efficiency of local anesthesia. Optimal outcomes for the mother and fetus hinge on a robust understanding of the physiologic alterations and the appropriate selection of anesthetic drugs and approaches.

Incidence and Survival of Oral Cavity and Oropharyngeal Cancer in the United States From 1975 to 2018.

PURPOSE: Oral cavity and oropharyngeal cancer (OC-OPC) is one of the most common cancers in the world. A comprehensive investigation of the temporal changes in incidence, overall survival (OS), and associated factors of this disease may facilitate the formulation and modification of public health control measures. METHODS: This is a retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database (1975 to 2018). Average annual percentage change (APC) in incidence was calculated by linear regression. Associations of incidence and OS with time and covariates (age, race, gender, site, grade, income, and residence) were analyzed. The Kaplan-Meier log-rank test was used for analysis of OS. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by Cox regression models. RESULTS: This study included 92,685 patients diagnosed with OC-OPC in Surveillance, Epidemiology, and End Results 9 database. An overall decrease was discovered in the incidence, especially among the Black population (APC, -15.2; 95% CI, -17.5 to -13.0; P < .01), and among those at 60+ years of age (APC, -12.8; 95% CI, -18.6 to -7.0; P < .01). Notably, the incidence among the rural population (APC, 7.1; 95% CI, 4.4 to 9.8; P < .01) increased. Residence and gender had the greatest effect on changes in incidence. Univariate analysis showed that the prognosis was worse in patients diagnosed between 1975 and 2000, patients from the Black population (HR, 1.87; 95% CI, 1.81 to 1.93; P < .01), patients at 60+ years of age (HR, 1.64; 95% CI, 1.61 to 1.68; P < .01), and patients with OPC. Interestingly, multivariate analysis showed no significant difference between OPC and OC, and the results of other subgroups were similar to univariate analysis. CONCLUSION: The results of this study indicate that more attention should be paid to facilitating OC-OPC prevention in rural population, as well as improving management of this disease in Black and elderly populations, and among patients with higher grade of disease and lower income.

Non-coding RNAs in exosomes and adipocytes cause fat loss during cancer cachexia.

Cancer Cachexia (CC) is a disease that changes various metabolisms in human body. Fat metabolism is significantly affected in CC, leading to fat loss. Non-coding RNAs (ncRNAs) in adipocytes and exosomes secreted by tumor play an important role in fat loss. However, there is no related reviews summarizing how ncRNAs contribute to fat loss during CC. This review screens recent articles to summarize how ncRNAs are packaged, transported in exosomes, and play the role in fat loss. Not only does this review summarize the mechanisms, we also point out the research orientations in the future.

The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia.

Cancer cachexia (CC) is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80% of patients with cancer; however, timely diagnostic methods and effective cures are lacking. Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy, few novel therapies have been applied in the last decade. In recent years, noncoding RNAs (ncRNAs) have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis. In addition, extracellular vesicles (EVs), which function as ncRNA carriers in intercellular communication, are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting; thus, EV-related ncRNAs may represent potential therapeutic targets. This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.

Cooperative N-H bond activation by amido-Ge(ii) cations.

N-heterocyclic carbene (NHC) and tertiary phosphine-stabilized germylium-ylidene cations, [R(L)Ge:]+, featuring tethered amido substituents at R have been synthesized via halide abstraction. Characterization in the solid state by X-ray crystallography shows these systems to be monomeric, featuring a two-coordinate C,N- or P,N-ligated germanium atom. The presence of the strongly Lewis acidic cationic germanium centre and proximal amide function allows for facile cleavage of N-H bonds in 1,2-fashion: the products resulting from reactions with carbazole feature a tethered secondary amine donor bound to a three-coordinate carbazolyl-GeII centre. In each case, addition of the components of the N-H bond occurs to the same face of the germanium amide function, consistent with a coordination/proton migration mechanism. Such as sequence is compatible with the idea that substrate coordination via the pπ orbital at germanium reduces the extent of N-to-Ge π donation from the amide, thereby enhancing the basicity of the proximal N-group.

Mild sp2Carbon-Oxygen Bond Activation by an Isolable Ruthenium(II) Bis(dinitrogen) Complex: Experiment and Theory.

The isolable ruthenium(II) bis(dinitrogen) complex [Ru(H)2(N2)2(PCy3)2] (1) reacts with aryl ethers (Ar-OR, R = Me and Ar) containing a ketone directing group to effect sp2C-O bond activation at temperatures below 40 °C. DFT studies support a low-energy Ru(II)/Ru(IV) pathway for C-O bond activation: oxidative addition of the C-O bond to Ru(II) occurs in an asynchronous manner with Ru-C bond formation preceding C-O bond breaking. Alternative pathways based on a Ru(0)/Ru(II) couple are competitive but less accessible due to the high energy of the Ru(0) precursors. Both experimentally and by DFT calculations, sp2C-H bond activation is shown to be more facile than sp2C-O bond activation. The kinetic preference for C-H bond activation over C-O activation is attributed to unfavorable approach of the C-O bond toward the metal in the selectivity determining step of the reaction pathway.