Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To investigate the correlation analysis of serum autotaxin(ATX),tenascin-C(TN-C)and ventricular remodeling indexes in elderly patients with dilated cardiomyopathy(DCM)with heart fail-ure(HF)and their effects on prognosis.Methods 153 elderly patients with DCM with HF who were admit-ted to the 904th Hospital of the Joint Logistic Support Force from January 2020 to January 2022 were selected as DCM with HF group,and 100 elderly patients with simple DCM in the same hospital during the same peri-od were selected as DCM group and 100 healthy elderly individuals who underwent physical examination were selectedas control group.Serum ATX and TN-C levels were detected by enzyme-linked immunosorbent assay,and ventricular remodeling indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular end-sys-tolic diameter(LVESD),and left ventricular ejection fraction(LVEF)]were detected by echocardiography.The correlation between serum ATX,TN-C levels and ventricular remodeling indexes in elderly patients with DCM with HF were analyzed by Pearson correlation analysis.Elderly patients with DCM with HF were fol-lowed up for 1 year,patients were divided into poor prognosis group and good prognosis group according to the prognosis.The influencing factors of poor prognosis in elderly patients with DCM with HF were analyzed by univariate and multivariate logistic regression analysis,the predictive value of serum ATX and TN-C levels for poor prognosis in elderly patients with DCM with HF was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of ATX and TN-C in DCM combined HF group were higher than those in DCM group and control group,and the difference was statistically significant(P＜0.05).Serum ATX and TN-C levels in DCM group were higher than those in control group,and the difference was statistically significant(P＜0.05).LVEDD and LVESD in DCM with HF group were higher than those in DCM group and control group,and LVEF was lower than those in DCM group and control group,the difference was statis-tically significant(P＜0.05).Pearson correlation analysis showed that serum ATX and TNC levels in elderly patients with DCM with HF were positively correlated with LVEDD and LVESD,and negatively correlated with LVEF(P＜0.05).Univariate analysis showed that HF disease course,NYHA cardiac function grade,NT-proBNP,ATX and TN-C were the influential factors for poor prognosis in elderly patients with DCM with HF(P＜0.05).Multivariate Logistic regression analysis showed that the independent risk factors for poor prognosis in elderly patients with DCM with HF were NYHA cardiac function grade≥Ⅲ and the increase of NT-proBNP,ATX and TN-C(P＜0.05).ROC curve analysis showed that the area under the curve and 95％CI of serum ATX and TNC alone and combined for poor prognosis in elderly patients with DCM with HF were 0.743(0.576-0.911),0.721(0.551-0.911)and 0.808(0.690-0.912),respectively.Conclusion The elevated levels of serum ATX and TN-C in elderly patients with DCM with HF may be relat-ed to ventricular remodeling and poor prognosis,and have certain predictive value for the prognosis of elderly patients with DCM with HF.

ObjectiveTo conduct a systematic review of the effect of active music therapy on cognitive function for older adults with cognitive impairment based on International Classification of Diseases, the 11th Revision (ICD-11), and International Classification of Functioning, Disability and Health (ICF). MethodsA PICO framework was constructed. Thematic keyword searches were conducted in databases including PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang data, for literature on the effect of active music therapy on cognitive function for older adults with cognitive impairment, published up to November 5th, 2023. Information on authors, countries, publication date, sample characteristics, study designs, intervention methods, measurement tools and outcomes were extracted. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. ResultsEight researches from six countries were included, which were all randomized controlled trials involving 356 older adults with mild cognitive impairment and dementia. The articles were published from 2014 to 2020, with an average of 7.4 of the PEDro scale. Active music therapy was used by singing and playing instruments. Interventions took place in hospitals, nursing homes, and health centers. The intervention duration ranged from mostly 30 to 60 minutes a time, with a few 120 minutes a time. Interventions were implemented mostly one to three times a week, lasting from eight to twelve weeks. Health outcomes focused on cognitive function, including overall cognitive function, executive function, attention function and memory function. ConclusionA theoretical framework for the benefits of active music therapy on the cognitive function for older adults with cognitive impairment has been constructed based on ICD-11 and ICF. Active music therapy can improve overall cognitive function, executive function, attention function and memory function for older adults with cognitive impairment.

ObjectiveTo conduct a systematic review of the health benefits of mindfulness interventions for older adults with insomnia disorders. MethodsThematic keyword search was conducted in databases including Web of Science, PubMed, Embase, EBSCO, CNKI, VIP and Wanfang data, for literature on the impact of mindfulness intervention on sleep quality in older adults with insomnia disorders, published up to August, 2023. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. Insomnia disorders, sleep function and mindfulness interventions were coded using International Classification of Diseases 11th Revision, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions Beta-3； and a systematic review was conducted following the PRISMA. ResultsNine researches from four countries were included, involving 800 participants, and all the researches were randomized controlled trials. The average score of PEDro scale was 7.1. The health-related conditions were insomnia disorders and insomnia disorders complicated with mild cognitive impairment. Mindfulness interventions used included mindfulness-based therapy for insomnia, mindfulness-based stress reduction, mindfulness-based cognitive therapy and mindfulness meditation. Interventions were implemented in institutions or health centers, care facilities, and community health service centers, varying from six to eight weeks. Health benefits of mindfulness intervention included improvements in sleep quality and psychological and behavioral health. ConclusionMindfulness interventions effectively improve sleep quality in older adults with insomnia disorders, alleviate negative emotional states such as depression, anxiety and perceived stress, and improve the quality of life.

Objective:To evaluate the efficacy and safety of intensity modulated radiotherapy (IMRT) and programmed death-1 (PD-1) immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods:Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed. IMRT was delivered at 1.8-2.0 Gy per fraction, 5 fractions per week, with a total dose of 45.0-60.0 Gy in 40 patients (IMRT group). The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy (PD-1 immunotherapy combined with single-agent chemotherapy group). Kaplan-Meier method was used for univariate analysis and the cumulative survival probability. Log-rank test was used for survival significance test. Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival (OS), progression-free survival (PFS) and local control (LC).Results:By December 2023, the follow-up rate was 100%. The 1- and 2-year OS rates in the IMRT group were 66.1% and 18.9%, with a median OS time of 10.1 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year OS rates were 72.3% and 36.9%, with a median OS time of 12.4 months. There was a significant difference in OS rates between two groups ( χ2=3.89, P=0.049). The 1- and 2-year PFS rates in the IMRT group were 47.4% and 31.6%, with a median PFS time of 8.5 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year PFS rates were 70.0% and 64.2%, with a median PFS time of 11.9 months. There was no significant difference in the PFS rates between two groups ( χ2=2.66, P=0.103). The 1- and 2-year LC rates in the IMRT group were 68.6% and 62.3%, with a median LC time of 8.9 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year LC rates were 72.8% and 66.7%, with a median LC time of 12.0 months. There was no significant difference in LC rates between two groups ( χ2=0.18, P=0.672). Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5% (33/40) and 32.5% (13/40) in the IMRT group, respectively. The incidence of grade 1-2 peripheral blood leukopenia was 40.0% (16/40), 50.0% (20/40) for grade 1-2 peripheral blood thrombocytopenia, 27.5% (11/40) for moderate to severe anemia, and 20.0% (8/40) for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy, respectively. Single- and multi-factor analysis showed that the failure site ( χ2=9.01, P=0.011) and short-term efficacy ( χ2=7.78, P=0.005) were the independent prognostic factors affecting OS. The short-term efficacy was the independent prognostic factor for PFS ( χ2=31.63, P<0.001). The short-term efficacy was the independent prognostic factors affecting LCS ( χ2=17.64, P=0.001) too. Conclusion:For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy, the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone, but it is still necessary to pay attention to the related drug toxicities.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment. Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.