Suppression of the NLRP3 Inflammasome through Activation of the Transient Receptor Potential Channel Melastatin 2 Promotes Osteogenesis in Tooth Extraction Sockets of Periodontitis.

This study explored the role of transient receptor potential channel melastatin 2 (TRPM2)-mediated activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in osteogenesis during healing of tooth extraction sockets. Tooth extraction socket tissue samples were collected from patients with or without periodontitis. In a TRPM2 knockout mouse model of socket healing, mice with or without periodontitis and their wild-type littermates were used for comparing the socket healing phenotypes. Micro-computed tomography imaging, three-dimensional reconstruction of the sockets, and hematoxylin and eosin staining for histopathologic analysis were performed. Immunofluorescence, immunohistochemistry, and Western blot analysis were used for evaluation of protein expression; the mRNA levels were evaluated by quantitative RT-PCR. Osteogenic, chondrogenic, and adipogenic differentiation potential of human bone marrow mesenchymal stem cells (BMMSCs) was evaluated. Calcium deposition was evaluated using Alizarin Red S staining. NLRP3 and CASP1 were up-regulated in tooth sockets of periodontitis patients. NLRP3 knockdown promoted the osteogenic differentiation of maxillary BMMSCs under inflammatory conditions. TRPM2 was up-regulated in the tooth extraction socket tissue of periodontitis. Inhibiting TRPM2 expression mitigated the NLRP3 inflammasome and its deleterious effect on osteogenesis. Activation of the TRPM2 ion channel regulated osteogenesis of BMMSCs under inflammatory conditions via Ca2+ influx, the mitochondrial dynamics, and pyroptosis. Targeting the TRPM2/Ca2+/NLRP3 axis could be beneficial in the healing process of the tooth extraction sockets of patients with periodontitis.

Positive effects of napping on memory consolidation and resistance against interference.

PURPOSE: This study explored the relationship between naps and memory among habitual nappers in China. METHODS: Medical college students participated and were divided into 30-min, 60-min, and 90-min time-in-bed groups. To evaluate declarative and procedural memory performance, A-B and A-C interfering word pair and interfering finger tapping tasks were employed. RESULTS: Among 60 students, a significant decrease in the correct recall rate in the declarative task after having a nap was found only in the 30-min group (p = 0.005). After learning interference (A-C word pairs), the correct recall rate for the declarative task decreased significantly in all interference tests (ps < 0.001). In the procedural task, the speed of sequence A in the retests increased after having a nap in all three groups (ps < 0.048), with a significant decrease in accuracy only in the 30-min group (p = 0.042). After learning interference (sequence B) in the procedural task, the speed of sequence A increased in the 60-min group after 1 h (p = 0.049), and both the 60-min and 90-min groups showed increased speed after one night (ps < 0.022). No significant improvement in speed was found in the 30-min group (ps > 0.05), and this group showed the lowest accuracy for sequence A (ps < 0.16). CONCLUSION: A habitual nap time-in-bed of 60 or 90 min had better effects on declarative and procedural memory consolidation and better memory resistance against interference in procedural memory.

Changes in sleep quality among Chinese active service personnel: A cross-temporal meta-analysis, 2003-2019.

Military personnel live in operating environments in which poor sleep is common. In this cross-temporal meta-analysis (CTMA), 100 studies (144 data sets, N = 75,998) were identified to examine changes in sleep quality among Chinese active service personnel from 2003 to 2019. Participants were divided into three groups: the navy, the non-navy, and the unknown service. The Pittsburgh Sleep Quality Index (PSQI) was used as the measure of sleep quality; it contains a global score and seven component scores, with higher scores indicative of poorer sleep. Among all active military personnel, the PSQI global and seven component scores decreased from 2003 to 2019. In examining the results by military type, the PSQI global and seven component scores increased in the navy group. Conversely, both the non-navy and unknown-service groups showed decreased PSQI global scores over time. Similarly, all PSQI component scores decreased over time for both the non-navy and unknown service groups, except for the use of sleeping medication (USM), which increased in the non-navy group. In conclusion, the sleep quality of Chinese active service personnel showed a positive trend. Further research should focus on improving the navy's sleep quality.

3D Orientation Imaging of Polymer Chains with Polarization-Controlled Coherent Raman Microscopy.

Despite the ubiquity of three-dimensional (3D) anisotropic materials, their 3D molecular alignment cannot be measured using conventional two-dimensional (2D) polarization imaging. Here, we present images of the 3D angles of molecular orientations with submicrometer spatial resolution acquired through polarization-controlled coherent anti-Stokes Raman scattering microscopy. The hyperspectral Raman data of a polyethylene (PE) film were converted into images, showing the polymer chains' 3D angles and order parameters. The 3D orientation images of PE chains in ring-banded spherulites show that the azimuthal angles of the chains are perpendicular to the crystal growth direction, while the out-of-plane angles display limited-range oscillations synchronous with ring banding. The prevailing crystal growth model of fully twisting lamellae is inconsistent with the observed restricted oscillations of the out-of-plane direction, which are unobservable through conventional 2D projected imaging. This high-resolution, label-free, quantitative imaging of 3D molecular orientation can become a standard measurement tool for the microscopic structures of complex synthetic and biological materials.

Imaging 3D molecular orientation by orthogonal-pair polarization IR microscopy.

Anisotropic molecular alignment occurs ubiquitously and often heterogeneously in three dimensions (3D). However, conventional imaging approaches based on polarization can map only molecular orientation projected onto the 2D polarization plane. Here, an algorithm converts conventional polarization-controlled infrared (IR) hyperspectral data into images of the 3D angles of molecular orientations. The polarization-analysis algorithm processes a pair of orthogonal IR transition-dipole modes concurrently; in contrast, conventional approaches consider individual IR modes separately. The orthogonal-pair polarization IR (OPPIR) method, introduced theoretically but never demonstrated experimentally, was used to map the 3D orientation angles and the order parameter of the local orientational distribution of polymer chains in a poly(ε-caprolactone) film. The OPPIR results show that polymer chains in the semicrystalline film are aligned azimuthally perpendicular to the radial direction of a spherulite and axially tilted from the film normal direction. This newly available information on the local alignments in continuously distributed molecules helps to understand the molecular-level structure of highly anisotropic and spatially heterogeneous materials.

N6-methyladenosine-related lncRNAs identified as potential biomarkers for predicting the overall survival of Asian gastric cancer patients.

OBJECTIVE: Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. METHODS: First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. RESULTS: We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters (p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4+ T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4+ T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. CONCLUSIONS: The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.

Compensation of Strong Water Absorption in Infrared Spectroscopy Reveals the Secondary Structure of Proteins in Dilute Solutions.

Infrared (IR) absorption spectroscopy is a powerful tool that can quantify complex biomolecules and their structural conformations. However, conventional approaches to protein analysis in aqueous solutions have been significantly challenged because the strong IR absorption of water overwhelms the limited dynamic range of the detection system and thus allows only a very short path length and a limited concentration sensitivity. Here, we demonstrate a solvent absorption compensation (SAC) approach that can improve the concentration sensitivity and extend the available path length by distinguishing the analyte signal over the full dynamic range at each wavelength. Absorption spectra without any postprocessing show good linearity from 100 to 0.1 mg/mL protein concentration, allowing a >100 times enhanced signal-to-noise ratio in the amide I band compared to the non-SAC results. We apply this method to in situ investigate the isothermal kinetics of insulin fibrillation at two clinical concentrations at 74 °C for 18 h. Simultaneous monitoring of both reactants (native forms) and products (fibrils) allows quantitative discussion of the detailed fibrillation mechanisms, which are not accessible with other single modality measurements. This simple optical technique can be applied to other absorption spectroscopies of analytes in strongly absorbing solvents, allowing for enhanced sensitivity without changing the detection system.

Prognostic value of a novel glycolysis-related gene expression signature for gastrointestinal cancer in the Asian population.

BACKGROUND: Globally, gastrointestinal (GI) cancer is one of the most prevalent malignant tumors. However, studies have not established glycolysis-related gene signatures that can be used to construct accurate prognostic models for GI cancers in the Asian population. Herein, we aimed at establishing a novel glycolysis-related gene expression signature to predict the prognosis of GI cancers. METHODS: First, we evaluated the mRNA expression profiles and the corresponding clinical data of 296 Asian GI cancer patients in The Cancer Genome Atlas (TCGA) database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL and TCGA-READ). Differentially expressed mRNAs between GI tumors and normal tissues were investigated. Gene Set Enrichment Analysis (GSEA) was performed to identify glycolysis-related genes. Then, univariate, LASSO regression and multivariate Cox regression analyses were performed to establish a key prognostic glycolysis-related gene expression signature. The Kaplan-Meier and receiver operating characteristic (ROC) curves were used to evaluate the efficiency and accuracy of survival prediction. Finally, a risk score to predict the prognosis of GI cancers was calculated and validated using the TCGA data sets. Furthermore, this risk score was verified in two Gene Expression Omnibus (GEO) data sets (GSE116174 and GSE84433) and in 28 pairs of tissue samples. RESULTS: Prognosis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1) among the differentially expressed glycolysis-related genes were screened and identified. The five-gene expression signature was used to assign patients into high- and low-risk groups (p < 0.05) and it showed a satisfactory prognostic value for overall survival (OS, p = 6.383 × 10-6). The ROC curve analysis revealed that this model has a high sensitivity and specificity (0.757 at 5 years). Besides, stratification analysis showed that the prognostic value of the five-gene signature was independent of other clinical characteristics, and it could markedly discriminate between GI tumor tissues and normal tissues. Finally, the expression levels of the five prognosis-related genes in the clinical tissue samples were consistent with the results from the TCGA data sets. CONCLUSIONS: Based on the five glycolysis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1), and in combination with clinical characteristics, this model can independently predict the OS of GI cancers in Asian patients.

Genetic polymorphisms and haplotypes of ERCC1 and ERCC2 associated with quality of life, depression, and anxiety status among patients with lung cancer.

BACKGROUND: Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC. METHODS: QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis. RESULTS: ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009). CONCLUSION: After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients.

Knowledge of a cancer diagnosis is a protective factor for the survival of patients with breast cancer: a retrospective cohort study.

BACKGROUND: The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival is not fully understood. This retrospective cohort study aims to explore the association between early informed diagnosis and survival time in breast cancer patients. METHODS: A total of 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors, including knowing the cancer diagnosis status, sex, age, clinical stage, surgery history, grade of reporting hospital and diagnostic year were, analyzed. We followed up all participants every 6 months until June 2017. Propensity score matching (PSM) was used to balance the clinicopathologic characteristics between patients who knew their diagnosis and those who did not. RESULTS: By June 2017, 18.04% of the participants died of breast cancer. Before PSM, both the 3-year and 5-year survival rates of patients who knew their cancer diagnosis were longer (P < 0.001). After PSM, the above conclusion was still established. By stratified analysis, except for the subgroups of male patients and stage III patients, patients who knew their diagnosis showed a better prognosis in all the other subgroups (P < 0.05). Cox regression analysis showed that knowing a cancer diagnosis was an independent risk factor for survival in breast cancer patients (P < 0.001). CONCLUSIONS: Being aware of their cancer diagnosis plays a protective role in extending the survival time of breast cancer patients, which suggests that medical staff and patients' families should disclose the cancer diagnosis to patients in a timely manner. Further prospective studies need to be made to validate our findings.

NIR-II emissive AIEgen photosensitizers enable ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors.

Accurate diagnosis and effective treatment of primary liver tumors are of great significance, and optical imaging has been widely employed in clinical imaging-guided surgery for liver tumors. The second near-infrared window (NIR-II) emissive AIEgen photosensitizers have attracted a lot of attention with higher-resolution bioimaging and deeper penetration. NIR-II aggregation-induced emission-based luminogen (AIEgen) photosensitizers have better phototherapeutic effects and accuracy of the image-guided surgery/phototherapy. Herein, an NIR-II AIEgen phototheranostic dot was proposed for NIR-II imaging-guided resection surgery and phototherapy for orthotopic hepatic tumors. Compared with indocyanine green (ICG), the AIEgen dots showed bright and sharp NIR-II emission at 1250 nm, which extended to 1600 nm with high photostability. Moreover, the AIEgen dots efficiently generated reactive oxygen species (ROS) for photodynamic therapy. Investigations of orthotopic liver tumors in vitro and in vivo demonstrated that AIEgen dots could be employed both for imaging-guided tumor surgery of early-stage tumors and for 'downstaging' intention to reduce the size. Moreover, the therapeutic strategy induced complete inhibition of orthotopic tumors without recurrence and with few side effects.

Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (DMRs) were identified near genes dysregulated in RPL including PRDM1. Differentially expressed genes were enriched in immune response pathways indicating that abnormal immune regulation contributes to RPL. Integrated analysis of DNA methylome and transcriptome demonstrated that the expression level of PRDM1 is fine-tuned by DNA methylation. Specifically, hypomethylation near the transcription start site of PRDM1 can recruit other transcription factors, like FOXA1 and GATA2, leading to up-regulation of gene expression and resulting in changes to trophoblast cell apoptosis and migration. These phenotypic differences may be involved in RPL. Overall, our study provides new insights into PRDM1-dependent regulatory effects during RPL and suggests both a mechanistic link between changes in PRDM1 expression, as well as a role for PRDM1 methylation as a potential biomarker for RPL diagnosis.

Heterogeneity of fibroblasts from radicular cyst influenced osteoclastogenesis and bone destruction.

AIM: To analyze the heterogeneity of fibroblasts isolated from the fibrous capsules of radicular cysts and explore the effects of fibroblast subsets on bone destruction. METHODOLOGY: Radicular cysts were divided into groups according to varying perilesional sclerosis identified by radiograph. Colony-forming units (CFUs) were isolated from the fibrous capsules of cysts, by which Trap + MNCs were induced, and the expression of osteoclastogenesis-related genes was compared among groups by real-time PCR. The variances in gene profiles of CFUs were identified by principal component analysis, and then, CFUs were divided into subsets using cluster analysis. The induction of Trap + MNCs and related gene expression was compared among subsets, and osteoclastogenic induction was blocked by IST-9 or bevacizumab. The fibroblast subsets in cysts were investigated by retrospective immunostaining with IST-9, VEGF-A, and CD34. A fibroblast subset that underwent gene editing by CRISPR/Cas was injected into the site of bone defects in animal models, and the in vivo effects on osteoclastogenesis were investigated. RESULTS: The fibroblast CFUs isolated from radicular cysts with perilesional unsclerotized cysts induced more Trap + MNCs than those with perilesional sclerotic cysts (p < .05). Most fibroblast CFUs from unsclerotized cysts belonged to Cluster 2, which induced more Trap + MNCs (p < .05) and highly expressed genes facilitating osteoclastogenesis; these results were different from those of Cluster 1 (p < .05), in which most CFUs were isolated from perilesional sclerotic cysts or controls (p < .05). The high expression of EDA + FN and VEGF-A was investigated in both the fibroblasts of Cluster 2 and the fibrous capsules of unsclerotized cysts (p < .05), and the number of Trap + MNCs induced by Cluster 2 was decreased by treatment with IST-9 and bevacizumab (p < .05). Consistently, EDA exon exclusion significantly decreased the osteoclastogenic induction of fibroblasts from Cluster 2 in vivo (p < .05). CONCLUSION: The fibrous capsules of radicular cysts contain heterogeneous fibroblasts that can form subsets exhibiting different effects on osteoclastogenesis. The subset, which depending on the autocrine effects of EDA + FN on VEGF-A, mainly contributes to the osteoclastogenesis and bone destruction of radicular cysts. The regulation of the proportion of subsets is a possible strategy for artificially interfering with osteoclastogenesis.

Rat sinus mucosa- and periosteum-derived exosomes accelerate osteogenesis.

Guided bone regeneration (GBR) is commonly used for alveolar bone augmentation. The paracrine mechanism in the field of bone tissue engineering has been emphasized in recent years and exosomes are considered to have the potential of promoting osteogenesis. We aimed to study the influence of sinus mucosa and periosteum on bone regeneration through paracrine stimulation, especially via exosomes, and compare the differences between them. Here, we report that conditioned medium (CM) from sinus mucosa-derived cells (SMCs) and periosteum-derived cells (PCs) and the isolated exosomes enhanced the proliferation, migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) in vitro. A rat model of femoral bone defects was used to demonstrate that the exosomes derived from SMCs (SMC-Exos) and PCs (PC-Exos) can accelerate bone formation in vivo. Furthermore, we present a preliminary discussion of the possible functional components involved in the effects of SMC-Exos and PC-Exos on bone regeneration. In conclusion, these results demonstrated that the sinus mucosa and periosteum can accelerate osteogenesis through paracrine effects and the exosomes play important roles in this process.

Unique Surface Enhanced Raman Scattering Substrate for the Study of Arsenic Speciation and Detection.

In this study, a three-dimensional surface enhanced Raman scattering (SERS) substrate comprised of silver coated gold nanorods (Ag/AuNRs) decorated on electrospun polycaprolactone (PCL) fibers has been applied,  for the first time, to quantitative analytical measurements on various arsenic species: p-arsanilic acid ( pAsA), roxarsone (Rox), and arsenate (AsV), with a demonstrated sensitivity below 5 ppb. AsV detection in a solution of common salt ions has been demonstrated, showing the tolerance of the substrate to more complex environments. pAsA adsorption behavior on the substrate surface has been investigated in detail using these unique SERS substrates. Calculations based on density functional theory (DFT) support the spectral observation for pAsA. This substrate also has been shown to serve as a platform for in situ studies of arsenic desorption and reduction. This SERS substrate is potentially an excellent environmental sensor for both fundamental studies and practical applications.

Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2 diabetes induced by high-fat diet and streptozotocin.

CONTEXT: Salvia miltiorrhiza Bge. (Labiatae) has been widely used for treating diabetes for centuries. Salvianolic acid B (SalB) is the main bioactive component in Salvia miltiorrhiza; however, its antidiabetic activity and possible mechanism are not yet clear. OBJECTIVE: To investigate the effects of SalB on glycometabolism, lipid metabolism, insulin resistance, oxidative stress, and glycogen synthesis in type 2 diabetic rat model. MATERIALS AND METHODS: High-fat diet (HFD) and streptozotocin-induced diabetic rats were randomly divided into model group, SalB subgroups (50, 100, and 200 mg/kg), and rosiglitazone group. RESULTS: Compared with the model group, SalB (100 and 200 mg/kg) significantly decreased blood glucose (by 23.8 and 21.7%; p < 0.05 and p < 0.01) and insulin (by 31.3 and 26.6%; p < 0.05), and increased insulin sensitivity index (by 10.9 and 9.3%; p < 0.05). They also significantly decreased total cholesterol (by 24.9 and 27.9%; p < 0.01), low-density lipoprotein cholesterol (by 56.2 and 64.6%; p < 0.01), non-esterified fatty acids (by 32.1 and 37.9%; p < 0.01), hepatic glycogen (by 41.3 and 60.5%; p < 0.01), and muscle glycogen (by 33.2 and 38.6%; p < 0.05), and increased high-density lipoprotein cholesterol (by 50.0 and 61.4%; p < 0.05 and p < 0.01), which were originally altered by HFD and streptozotocin. In addition, SalB (200 mg/kg) markedly decreased triglyceride and malondialdehyde (by 31.5 and 29.0%; p < 0.05 and p < 0.01), and increased superoxide dismutase (by 56.6%; p < 0.01), which were originally altered by HFD and streptozotocin. DISCUSSION AND CONCLUSION: The results indicate that SalB can inhibit symptoms of diabetes mellitus in rats and these effects may partially be correlated with its insulin sensitivity, glycogen synthesis and antioxidant activities.

Salvianolic acid B inhibited PPARγ expression and attenuated weight gain in mice with high-fat diet-induced obesity.

BACKGROUND/AIMS: Obesity contributes to the development of cardiometabolic disorders such as type 2 diabetes, fatty liver disease and cardiovascular disease. Salvianolic acid B (Sal B) is a molecule derived from the root of Salvia miltiorrhiza (Danshen), which is a traditional Chinese medicine that is widely used to treat cardiovascular diseases. However, the role of Sal B in obesity and obesity-related metabolic disorders is unknown. In this study, we aimed to investigate the effects of Sal B on high-fat diet-induced obesity and determine the possible mechanisms involved. METHODS: Male C57BL/6J mice fed a high-fat diet for 12 weeks received a supplement of Sal B (100 mg/kg/day) by gavage for a further 8 weeks. These mice were compared to control mice fed an un-supplemented high-fat diet. 3T3-L1 preadipocytes were used in vitro studies. RESULTS: Sal B administration significantly decreased body weight, white adipose tissue weight, adipocyte size and lipid (triglyceride and total cholesterol) levels in obese mice. Eight weeks of Sal B administration also improved the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) scores in high-fat diet-induced obese mice. In 3T3-L1 preadipocytes that were cultured in vitro and induced to differentiate, Sal B reduced the accumulation of lipid droplets and lipid content in a dose-dependent manner. Immunoblotting indicated that Sal B decreased peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) expression but increased the expression of GATA binding protein 2 and 3 (GATA 2, GATA 3) both in vivo and in vitro. CONCLUSION: Our data suggest that Sal B may reduce obesity and obesity-related metabolic disorders by suppressing adipogenesis. The effects of Sal B in adipose tissue may be related to its action on PPARγ, C/EBPα, GATA-2 and GATA-3.

Qualitative and quantitative analysis of the major constituents in Jin-Mu-Gan-Mao tablet by high-performance liquid chromatography with diode-array detection and quadrupole time-of-flight tandem mass spectrometry.

Jin-Mu-Gan-Mao tablet is a well-known traditional Chinese medicinal preparation, which has been used to treat the common cold in China. In this study, a systematic method was established for the qualitative and quantitative analysis of the major constituents in Jin-Mu-Gan-Mao tablet. First, a method of high-performance liquid chromatography with diode-array detection and quadrupole time-of-flight mass spectrometry was developed for identification of the multi-constituents. Thirty-one compounds including ten phenolic acids, 18 flavonoids, and three iridoid glycosides were clearly identified by comparison with the reference standards, and 11 compounds were deduced by comparison with the literature data. Second, a new quantitative analysis method of Jin-Mu-Gan-Mao tablet was established by high-performance liquid chromatography with diode-array detection. Twelve compounds, either with high contents or strong bioactivities, were chosen as marker components. This analytical method was validated through intra- and interday precision, repeatability, and stability, with respective relative standard deviations less than 1.74, 2.54, 2.44, and 2.48%. The limits of detection and quantification were less than 0.327 and 0.881 µg/mL, respectively. The overall recoveries ranged from 97.04-102.76% (relative standard deviation ≤ 2.91%). Then this validated method was applied to determine ten batches of Jin-Mu-Gan-Mao tablet. The results indicated that these new approaches can be applicable for the qualitative and quantitative analysis of Jin-Mu-Gan-Mao tablet.

Identifying key variables in African American adherence to colorectal cancer screening: the application of data mining.

BACKGROUND: This paper reports on an effort to identify a streamlined set of issues important for colorectal cancer communication and interventions with older African Americans. METHODS: African American (N = 1,021), 683 women and 338 men, 50 to 75 years completed a telephone survey addressing demographics, colorectal cancer screening, cancer attitudes, and cancer related cultural attitudes. Several data analytics methods were applied and evaluated. Among them, results from associative data mining identified key variables and logistic regression was used to confirm associations to screening adherence. RESULTS: Sets of co-occurring variables identified by associative data mining methods are extracted to further study differences between adherent and non-adherent groups. Logistic regressions suggested four variables were significantly associated with adherence: healthcare provider colonoscopy recommendation, prevention services at the place health care is usually sought, a history of colitis, and a history of polyps. CONCLUSIONS: The findings suggest a streamlined set of issues and concerns that may be used by providers advising patients or developing colorectal cancer intervention strategies for older African Americans. The data suggest the continued importance of healthcare provider recommendation to screen. It is important that providers give a clear recommendation to screen regardless of the test ultimately selected and should advise all patients that family history and the absence of symptoms or colitis do not eliminate the value of screening.

The detection of Gper1 as an important gene promoting jawbone regeneration in the context of estrogen deficiency.

Numerous studies have demonstrated that estrogen deficiency inhibit the proliferation and differentiation of pre-osteoblasts in skeleton by affecting osteogenic signaling, lead to decreased bone mass and impaired regeneration. To explore the mechanisms maintaining bone regeneration under estrogen deficiency, we randomly selected 1102 clinical cases, in which female patients aged between 18 and 75 have underwent tooth extraction in Stomatological Hospital of Tongji University, there is little difference in the healing effect of extraction defects, suggesting that to some extent, the regeneration of jawbone is insensitive to the decreased estrogen level. To illuminate the mechanisms promoting jawbone regeneration under estrogen deficiency, a tooth extraction defect model was established in the maxilla of female rats who underwent ovariectomy (OVX) or sham surgery, and jawbone marrow stromal cells (BMSCs) were isolated for single-cell sequencing. Further quantitative PCR, RNA interference, alizarin red staining, immunohistochemistry and western blotting experiments demonstrated that in the context of ovariectomy, maxillary defects promoted G protein-coupled estrogen receptor 1 (Gper1) expression, stimulate downstream cAMP/PKA/pCREB signaling, and facilitate cell proliferation, and thus provided sufficient progenitors for osteogenesis and enhanced the regeneration capacity of the jawbone. Correspondingly, the heterozygous deletion of the Gper1 gene attenuated the phosphorylation of CREB, led to decreased cell proliferation, and impaired the restoration of maxillary defects. This study demonstrates the importance of Gper1 in maintaining jawbone regeneration, especially in the context of estrogen deficiency.