The impact of the P2X7 receptor on the tumor immune microenvironment and its effects on tumor progression.

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.

Multiplex Sensing Based on Plasmonic Optics of Noble Metallic Nanostructures.

Since the colorimetric method has the characteristics of being simple and low cost, the fluorescence spectrum has the characteristics of a strong signal, and Surface-enhanced Raman scattering (SERS) detection has the characteristics of high sensitivity and strong specificity, people usually use these three methods for detection, but the detection of a single sample takes more time. If multiple samples can be tested at the same time, the detection efficiency and sensitivity can be improved, and the selectivity and reliability will be greatly improved. Multiplex sensing also provides a new direction for researchers. To fully understand the research of multiplex sensing based on the plasmonic optics of noble metal nanostructures, this review summarizes all the results previously reported in this field. It also discusses the principles of various detection methods and the biochemical application of multiple detections and finally summarizes the challenges and prospects.

Comprehensive Analysis of CRIP1 Expression in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that imposes great challenges in terms of drug resistance and relapse. Previous studies revealed heterogeneous leukemia cells and their relevant gene markers, such as CRIP1 as clinically prognostic in t (8;21) AML patients. However, the expression and role of CRIP1 in AML are poorly understood. We used the single-cell RNA sequencing and gene expression data from t (8;21) AML patients to analyze the immune and regulation networks of CRIP1. Two independent cohorts from GSE37642 and The Cancer Genome Atlas (TCGA) datasets were employed as validation cohorts. In addition, the methylation data from TCGA were used to analyze the methylation effect of the CRIP1 expression. Gene expression profile from t (8;21) AML patients showed that the CRIP1-high group exhibited an enrichment of immune-related pathways, including tumor necrosis factor (TNF)α signaling via nuclear factor kappa B (NFκB) pathways. Further studies using CIBERSORT showed that the CRIP1-high group had a significantly higher infiltration of exhausted CD8 T cells and activated mast cells. The CRIP1 expression was validated in the GSE37642-GPL96, GSE37642-GPL570, and TCGA datasets. In addition, with the methylation data, four CpG probes of CRIP1 (cg07065217, cg04411625, cg25682097, and 11763800) were identified as negatively associated with the CRIP1 gene expression in AML patients. Our data provide a comprehensive overview of the regulation of CRIP1 expression in AML patients. The evaluation of the TNFα-NFκB signaling pathway as well as the immune heterogeneity might provide new insights for exploring improvements in AML treatment.

A prognostic survival model based on metabolism-related gene expression in plasma cell myeloma.

Accurate survival prediction of persons with plasma cell myeloma (PCM) is challenging. We interrogated clinical and laboratory co-variates and RNA matrices of 1040 subjects with PCM from public datasets in the Gene Expression Omnibus database in training (N = 1) and validation (N = 2) datasets. Genes regulating plasma cell metabolism correlated with survival were identified and seven used to build a metabolic risk score using Lasso Cox regression analyses. The score had robust predictive performance with 5-year survival area under the curve (AUCs): 0.71 (95% confidence interval, 0.65, 0.76), 0.88 (0.67, 1.00) and 0.64 (0.57, 0.70). Subjects in the high-risk training cohort (score > median) had worse 5-year survival compared with those in the low-risk cohort (62% [55, 68%] vs. 85% [80, 90%]; p < 0.001). This was also so for the validation cohorts. A nomogram combining metabolic risk score with Revised International Staging System (R-ISS) score increased survival prediction from an AUC = 0.63 [0.58, 0.69] to an AUC = 0.73 [0.66, 0.78]; p = 0.015. Modelling predictions were confirmed in in vitro tests with PCM cell lines. Our metabolic risk score increases survival prediction accuracy in PCM.

An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy.

PURPOSE: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. EXPERIMENTAL DESIGN: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. RESULTS: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. CONCLUSIONS: Our immune risk score complements current AML prediction models.

Analysis of the correlation between periodontal disease and metabolic syndrome among coal mine workers: A clinical study.

Metabolic syndrome (MetS) refers to the pathological state of metabolic disorders in the body's proteins, fats, carbohydrates and other substances. MetS is a systemic metabolic disease. Periodontal disease is also a part of systemic inflammatory diseases. Among Chinese patients with middle-aged and elderly MetS, the periodontal morbidity is very high, which is due to the involvement of inflammatory mediators in the pathogenesis of MetS and periodontal disease. The latter may also be a risk factor for the former's morbidity and promotion of disease progression. At present, there are not many investigations and studies on periodontal examination data and periodontal disease prevalence of patients with MetS. Coal mine workers, especially coal mine underground workers, have different work natures and different working environments. See related report.We will collect the clinical diagnosis and treatment information of the enrolled patients. We will focus on checking the incidence of periodontal disease and recording. Establish a database, check every 10 medical records, and make corrections in time to ensure data accuracy. We will popularize oral hygiene knowledge for the included patients and guide them to brush their teeth correctly and how to use dental floss. We will perform periodontal examination on the patients' teeth by site and record the plaque index, gingival sulcus bleeding index, periodontal pocket exploration depth and other indicators. We will repeat the above inspection items and record in the second and fourth weeks of the experiment.This study will explore the correlation between periodontal disease and MetS of coal mine workers. We aim to clarify the role and mechanism of MetS in the occurrence and development of periodontal diseases, guide the prevention of periodontal diseases, and thus reduce the prevalence of periodontal diseases. TRIAL REGISTRATION:: ClinicalTrials.gov, ChiCTR2000034177, Registered on 27 June 2020.

Systematic Construction and Validation of a Metabolic Risk Model for Prognostic Prediction in Acute Myelogenous Leukemia.

Background: Acute myelogenous leukemia (AML) is a heterogeneous disease with recurrent gene mutations and variations in disease-associated gene expression, which may be useful for prognostic prediction. Methods: RNA matrix and clinical data of AML were downloaded from GEO, TCGA, and TARGET databases. Prognostic metabolic genes were identified by LASSO analysis to establish a metabolic model. Prognostic accuracy of the model was quantified by time-dependent receiver operating characteristic curves and the area under the curve (AUC). Survival analysis was performed by log-rank tests. Enriched pathways in different metabolic risk statuses were evaluated by gene set enrichment analyses (GSEA). Results: We identified nine genes to construct a prognostic model of shorter survival in the high-risk vs. low-risk group. The prognostic model showed good predictive efficacy, with AUCs for 5-year overall survival of 0.78 (0.73-0.83), 0.76 (0.62-0.89), and 0.66 (0.57-0.75) in the training, adult external, and pediatric external cohorts, respectively. Multivariable analysis demonstrated that the metabolic signature had independent prognostic value with hazard ratios of 2.75 (2.06-3.66), 1.89 (1.09-3.29), and 1.96 (1.00-3.84) in the training, adult external, and pediatric external cohorts, respectively. Combining metabolic signatures and classic prognostic factors improved 5-year overall survival prediction compared to the prediction by classic prognostic factors (p < 0.05). GSEA revealed that most pathways were metabolism-related, indicating potential mechanisms. Conclusion: We identified dysregulated metabolic features in AML and constructed a prognostic model to predict the survival of patients with AML.

Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

[Changes of TGF-ß1 expression during orthodontic tooth movement in rats with osteoporosis].

PURPOSES: To observe the expression and distribution of TGF-ß1 in periodontal tissue under intervention of Strontium ranelate and Qianggu capsule during orthodontic tooth movement in rats, and explore the efficacy of the 2 drugs. METHODS: Seventy male SD rats of 3 months old were selected in the study, and randomly divided into control group, model control group, Strontium ranelate group, Qianggu capsule group, each group had 15 animals. Retinoic acid was given by gavage to animals in the control group, Strontium ranelate group, Qianggu capsule group for 2 weeks, and bone density was detected to determine successful establishment of osteoporosis model. All rats were installed orthodontic device, and were sacrificed at 7 days, 14 days and 21 days, respectively. The tissue blocks of the first maxillary molar and adjacent alveolar bone were taken for H-E staining, immunohistochemical staining and semi-quantitative analysis was used to detect TGF-ß1 expression in periodontal tissues. The data were statistically analyzed by SPSS 17.0 software package. RESULTS: TGF- beta 1 expression was significantly increased in Strontium ranelate group and Qianggu capsule group compared with control group (P<0.05); TGF- beta 1 expression in Strontium ranelate group was significantly stronger than that of Qianggu capsule group (P<0.05). CONCLUSIONS: Strontium ranelate and Qianggu capsule could enhance the expression of TGF- beta 1 and promote bone metabolism in osteoporosis rats, which is helpful to the movement of healthy teeth; the effect of Strontium ranelate is stronger than Qianggu capsule.

[The influence of different treating agents on the shear bond strength between zirconia and orthodontic brackets].

PURPOSE: To compare the effect of different treating agents on the shear bond strength (SBS) between zirconia and orthodontic brackets. METHODS: Fifty zirconia specimens were randomly divided into 5 groups(n=10), and treated with sandblasted and 37% phosphoric acid.Group A was control sample without any treatment; Group B was treated with silane coupling agent; Group C was treated with silane coupling agent and SE Bond; Group D were treated with Z-Prime(TM) Plus; Group E were treated with Z-Prime(TM) Plus+SE Bond. The upper incisor brackets were bonded to each specimen using 3M Transbond light-cured resin adhesive. Each specimen was put into 37°C water, and SBS tests were performed after 24 hours. Then statistical analysis was carried out regarding to the adhesive residual index(ARI) of the zirconia oxide surface after removing the brackets. The surface of zirconia in each group was scanned with scanning electron microscope after surface treatment, and the surface morphology changes were observed, infrared spectra analysis was conducted on zirconia and treating agents. SPSS 17.0 software package was utilized for statistical analysis. RESULTS: The mean SBS in each group was as follows: group A (3.12±0.84) MPa; group B (1.92±0.83) MPa; group C (5.26±0.80) MPa; group D (6.54±0.98) MPa; group E (9.47±2.11) MPa. Significant difference existed between each group (P<0.05), group A and B had lower ARI, while ARI in group E was highest. Group D and E achieved effective bond strength. CONCLUSIONS: Using Z-Prime(TM) Plus can achieve effective bond strength, which is lower than Z-Prime(TM) Plus combined with SE Bond. It's suggested to use Z-Prime(TM) Plus combined with SE Bond to achieve higher SBS for orthodontic treatment.

[Study on antimicrobial effect of the mixture of Chinese medicine-chitosan to Candida albicans and the possibility as denture adhesive].

PURPOSE: To observe the antimicrobial effect and the tensile bond strength of water-soluble chitosan after adding different Chinese medicines to Candida albicans. METHODS: The extract of 6 kinds of Chinese medicine by decoction in different concentrations were mixed with chitosan, and the most effective mixture inhibiting Candida albicans and the minimal inhibitory concentration (MIC) were explored; Then the tensile bond strength of the mixture was tested and compared with Protefix denture adhesive. The data was analyzed with SPSS17.0 software package. RESULTS: The antibacterial effect of polyphylla-chitosan mixture was the best among the 6 kinds of Chinese medicine- chitosan mixture, and its MIC was 1.563 mg/mL. The tensile bond strength of polyphylla-chitosan mixture at 0 h and 12 h when immersed in artificial saliva were significantly larger than Protefix denture adhesive. The average value and the maximum value was significantly greater than the Protefix denture adhesive (P<0.05). CONCLUSIONS: Polyphylla-chitosan mixture has good antibacterial effect on Candida albicans and large tensile bond strength.

Low-magnitude high-frequency loading, by whole-body vibration, accelerates early implant osseointegration in ovariectomized rats.

Osteoporosis deteriorates jaw bone quality and may compromise early implant osseointegration and early implant loading. The influence of low­magnitude, high­frequency (LMHF) vibration on peri­implant bone healing and implant integration in osteoporotic bones remains poorly understood. LMHF loading via whole­body vibration (WBV) for 8 weeks has previously been demonstrated to significantly enhance bone­to­implant contact, peri­implant bone fraction and implant mechanical properties in osteoporotic rats. In the present study, LMHF loading by WBV was performed in osteoporotic rats, with a loading duration of 4 weeks during the early stages of bone healing. The results indicated that 4­week LMHF loading by WBV partly reversed the negative effects of osteoporosis and accelerated early peri­implant osseointegration in ovariectomized rats.

Exceptional temperature-dependent coordination sites from acylamide groups.

Herein, through altering the reaction temperature, the coordination mode of the acylamide ligand is well controlled with or without the oxygen coordination site. The resulting two new coordination polymers have the formulas Cd3(L)2(bdc)3·4(H2O) (1) and Cd(L)(bdc)·2(H2O) (2) (L = N(1),N(4)-bis(pyridin-3-ylmethyl)terephthalamide, H2bdc = terephthalic acid).

Early healing of hydroxyapatite-coated implants in grafted bone of zoledronic acid-treated osteoporotic rabbits.

BACKGROUND: Resorption of grafted bone and delayed osseointegration of implants are main problems associated with alveolar bone augmentation in dental implantology, especially for patients with osteoporosis. The aim of this study is to investigate the early healing response of implants to systemic treatment of zoledronic acid (ZA) in autogenous grafted iliac bone of osteoporotic rabbits. METHODS: Ovariectomy (OVX) or sham operation was performed in 46 rabbits, and osteoporotic changes were verified in animals receiving OVX 3 months later. The remaining animals were divided into three groups (n = 12): sham, OVX, and OVX with ZA treatment (ZA group). Autogenous iliac bone grafting was performed in bilateral tibiae, and hydroxyapatite-coated titanium implants were simultaneously placed into the grafted bone. The animals were sacrificed 2 and 8 weeks later for examination. RESULTS: At both time points, systemic treatment of ZA efficiently promoted bone healing of implants in grafted bone, and all histologic and microcomputed tomography bone indices, including mineralized bone volume, implant-bone contact ratio, connectivity density, trabecular thickness, and trabecular number, were significantly increased in the ZA group compared with the OVX-only group (P <0.01); implant-bone contact rates in the ZA group were even restored to levels similar to those of sham-operated animals (P >0.05). Furthermore, biomechanical testing demonstrated that removal torque of implants was significantly increased in the ZA group compared with the OVX group (P <0.01). CONCLUSION: Systemic treatment with ZA could efficiently promote early bone healing of implants in autogenous grafted bone of osteoporotic rabbits by increasing early osseointegration and fixation of implants.

[Influence of zoledronate on osteoclast differentiation and gene expression of calmodulin and calmodulin-dependent protein kinase II].

OBJECTIVE: To investigate the effect of zoledronate acid on osteoclast differentiation and gene expression of calmodulin (CAM) and calmodulin-dependent protein kinase (CAMK)II. METHODS: Receptor activation of nuclear factor κB ligand (RANKL) was used to induce differentiation of RAW264.7 cells into osteoclasts in vitro. The cells were divided into two groups, group A and group B. Both groups were treated with RANKL for 5 days, whereas group B was also treated with zoledronate for the last 2 days.Osteoclastogenesis and gene expression of CAM and CAMK II were examined. RESULTS: In group B, the number of new-generated osteoclasts (≥3 nuclei), number and size of dentin resorption lacunaes were (23 ± 3) , (19 ± 2) and (4951 ± 223) µm(2) respectively, which were significantly lower than those [(44 ± 3) , (46 ± 1) and (13 331 ± 248) µm(2)] in group A (P < 0.01).mRNA and protein level of CAM and CAMK II were also significantly down-regulated in group B when compared with group A (P < 0.01) and the decrease was 26.7% and 37.2% respectively for CAM, 57.0% and 76.1% respectively for CAMK II. CONCLUSIONS: Zoledronate acid could significantly inhibit formation and resorption function of osteoclasts. CAM and CAMKII may be involved in the inhibition process.