HIV/HBV coinfection: understanding the complex interactions and their impact on spontaneous HBV clearance, chronic liver damage, cirrhosis, and hepatocellular carcinoma.

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies.

Analysis of intestinal flora and cognitive function in maintenance hemodialysis patients using combined 16S ribosome DNA and shotgun metagenome sequencing.

BACKGROUND: Cognitive impairment is widely prevalent in maintenance hemodialysis (MHD) patients, and seriously affects their quality of life. The intestinal flora likely regulates cognitive function, but studies on cognitive impairment and intestinal flora in MHD patients are lacking. METHODS: MHD patients (36) and healthy volunteers (18) were evaluated using the Montreal Cognitive Function Scale, basic clinical data, and 16S ribosome DNA (rDNA) sequencing. Twenty MHD patients and ten healthy volunteers were randomly selected for shotgun metagenomic analysis to explore potential metabolic pathways of intestinal flora. Both16S rDNA sequencing and shotgun metagenomic sequencing were conducted on fecal samples. RESULTS: Roseburia were significantly reduced in the MHD group based on both 16S rDNA and shotgun metagenomic sequencing analyses. Faecalibacterium, Megamonas, Bifidobacterium, Parabacteroides, Collinsella, Tyzzerella, and Phascolarctobacterium were positively correlated with cognitive function or cognitive domains. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included oxidative phosphorylation, photosynthesis, retrograde endocannabinoid signaling, flagellar assembly, and riboflavin metabolism. CONCLUSION: Among the microbiota, Roseburia may be important in MHD patients. We demonstrated a correlation between bacterial genera and cognitive function, and propose possible mechanisms.

Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID.

Objectives: To analyze the correlation between heart rate variability (HRV) and palpitation symptoms in female patients with long COVID. Methods: A total of 272 female healthcare workers who were infected with SARS-CoV-2 for the first time in December 2022 at Fuzhou First Hospital affiliated with Fujian Medical University, were selected as study subjects. These subjects were divided into three groups based on their symptoms: a group with palpitations (70 cases), a group without palpitations but with other symptoms (124 cases), and a group consisting of asymptomatic cases (78 cases). The study compared the general information, COMPASS-31 scores, quality of life scores, and HRV parameters among the three groups. Furthermore, it analyzed the factors influencing palpitation symptoms in female patients with long COVID. Results: Compared to the other two groups, the HRV parameters SDNN, HRVIndex, LF, and TP were significantly reduced in the group with palpitations (p < 0.05). Multivariate analysis revealed that HRVIndex (p = 0.016; OR: 0.966, 95% CI: 0.940∼0.994) had a significant impact on palpitation symptoms in female patients with long COVID. Conclusions: The symptoms of palpitations in female patients with long COVID were found to be related to HRV parameters. Autonomic dysfunction may be connected to the occurrence of palpitation symptoms in long COVID.

Influence of the In-Stream Structure on Solute Transport in the Hyporheic Zone.

The hyporheic zone (HZ) plays an important role in the river ecosystem, and hyporheic exchange and solute transport in the HZ are important ecological functions. However, the relationship between the design parameters of river structure and solute transport is still poorly understood. In this study, we combined flume experiments and numerical simulations to systematically evaluate how in-stream structures impact the solute transport depth (DP), hyporheic vertical exchange flux (Q), and solute flux (Qs). The results showed that the in-stream structure had a significant influence on solute transport in the HZ and could obviously increase the intensity of hyporheic exchange and promote solute transport. Model results indicated that DP, Q, and Qs increased with the ratio of ground height to underground height of structure (H/D) and structure number (N), while Q, DP, and Qs increased with the structural spacing (S) to begin with; then, Q remained constant, and DP and Qs decreased as S continued to increase. This study deepened our understanding of the influence of in-stream structural design parameters on HZ solute transport, which is helpful to provide a theoretical basis for ecological restoration projects in the river HZ.

NOD2 is involved in regulating odontogenic differentiation of DPSCs suppressed by MDP through NF-κB/p65 signaling.

Dental pulp stem cells (DPSCs) are well known for their capable of both self-renewal and multilineage differentiation. Dental tissue diseases, include caries, are often accompanied by inflammatory microenvironment, and muramyl dipeptide (MDP) is involved in the inflammatory stimuli to influence the differentiation of DPSCs. Nucleotide-binding oligomerization domain 2 (NOD2), a member of the cytosolic Nod-like receptor (NLR) family, plays a key role in inflammatory homeostasis regulation, but the role of NOD2 in DPSCs differentiation under inflammatory is still unclear. In this study, we identified that MDP suppressed odontogenic differentiation of DPSCs via NOD2/ NF-κB/p65 signaling pathway. Alizarin red staining and ALP activity showed the odontogenic differentiation was suppressed by MDP in a concentration-dependent manner, and the expression of dentin differentiation marker protein dentin matrix protein 1 (DMP-1) and dentin Sialophosphoprotein (DSPP) also indicated the same results. The expression of NOD2 increased gradually with the concentration of MDP as well as the phosphorylation and nuclear translocation of p65, which meant NF-κB signaling pathway was activated. Further, the interference of NOD2 inhibited the phosphorylation and nuclear translocation of p65 and reversed the MDP-mediated decrease of odontoblast differentiation of DPSCs. Our study showed that MDP can inhibit the odontoblast differentiation of DPSCs in a concentration-dependent manner. The NF-κB signaling pathway was activated by increasing expression of NOD2. Interference of NOD2 reversed the negative ability odontoblast differentiation of DPSCs in the inflammatory environment. Our study might provide a theoretical basis for the clinical treatment for dentinogenesis of DPSCs.

miR-153-3p inhibited osteogenic differentiation of human DPSCs through CBFß signaling.

Dental pulp stem cells (DPSCs) have multilineage differentiation potential and especially show a great foreground in bone regeneration engineering. The mechanism of osteogenic differentiation of DPSCs needs to be explored exactly. As a kind of endogenous and non-coding small RNAs, microRNAs (miRNAs) play an important role in many biological processes including osteogenic differentiation. However, the mechanism of miR-153-3p in osteogenic differentiation of DPSCs is still unknown. Core-binding factors-beta (CBFß) is a non-DNA-binding factor that combines with the runt-related transcription factor family transcription factors to mediate their DNA-binding affinities, and plays a critical role in regulating osteogenic differentiation. In this study, we explored the mechanisms of miR-153-3p and CBFß in DPSC osteogenesis. The expression of miR-153-3p and CBFß was tested under the osteogenic condition, and the influence led by changing the expression of miR-153-3p or CBFß had also been detected. A luciferase reporter assay confirmed that miR-153-3p directly targeted to CBFß. The osteogenic markers, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and bone morphogenetic protein 2 (BMP2), were tested in protein level or mRNA level. ALP and Alizarin red staining were used to detect the osteoblast activity and mineral deposition. In osteogenic condition, the expressions of CBFß and osteogenic markers were upregulated, whereas that of miR-153-3p was downregulated. miR-153-3p negatively regulated the osteogenic differentiation, and overexpression of CBFß could offset the negative effect of miR-153-3p. Our findings provided a novel strategy for DPSC application in treatment of bone deficiencies and facilitated bone regeneration.

General Control Nonrepressed Protein 5 Modulates Odontogenic Differentiation Through NF-κB Pathway in Tumor Necrosis Factor-α-Mediated Impaired Human Dental Pulp Stem Cells.

Dental pulp stem cells (DPSCs) from pulpitis patients showed defective osteogenic differentiation. However, as the most well-studied histone acetyltransferase, the impaired general control nonrepressed protein 5 (GCN5) plays essential roles in various developmental processes. The aim of this study was to investigate the effect of GCN5 on DPSCs odontogenic differentiation. The healthy dental pulp tissues were obtained from the extracted impacted third molar of patients with the informed consent. DPSCs were treated with a high concentration of tumor necrosis factor-alpha (TNF-α) (100 ng/mL) and odontogenic differentiation-related gene and GCN5 protein level by Western blot analysis. Proliferation of the DPSCs was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunofluorescence staining detected GCN5 and NF-κB signaling for p-p65. The mechanism of GCN5 regulating odontogenic differentiation of DPSCs was determined by small interfering RNA analysis. Our data suggested that TNF-α can significantly reduce mineralization and the expression of dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein at higher concentration (100 ng/mL). Meanwhile, it showed that the inflammation in microenvironment resulted in a downregulation of GCN5 expression and GCN5 knockdown caused decreased odontogenic differentiation of DPSCs was also found. In addition, the knockdown of GCN5 increased the expression of phosphorylation of p65, thus activating NF-κB pathway of DPSCs. Meanwhile, NF-κB pathway inhibitor pyrrolidinedithiocarbamic acid reversed the siGCN5 decreased odontogenic differentiation of DPSCs. Altogether, our findings indicated that in inflammatory microenvironments GCN5 plays a protective role in pulpitis impaired odontogenic differentiation of DPSCs by activating NF-κB pathway, which may provide a potential approach to dentin regeneration.

The efficacy and safety of Sacubitril/Valsartan in the treatment of chronic heart failure: a meta-analysis.

OBJECTIVE: A meta-analysis of the studies involving Sacubitril/Valsartan in chronic heart failure was performed to compare the efficacy and safety of Sacubitril/Valsartan with traditional drug therapy in chronic heart failure. METHODS: We searched databases from PubMed, EMBASE, the Cochrane Library, Web of Science, and clinicaltrials.gov for studies published between 2010 and 2020 that reported efficacy and safety following Sacubitril/Valsartan administration. RESULTS: Ten studies enrolling 1689 patients were included. Sacubitril/Valsartan outperformed traditional medicine (especially the Non-ARNI group) in terms of blood pressure, biomarkers and cardiac reverse remodeling indices, with striking changes in left ventricular ejection fraction, systolic blood pressure. Sacubitril/Valsartan showed significant benefit in renal function in patients with chronic heart failure. CONCLUSIONS: Compared with traditional drugs, Sacubitril/Valsartan significantly improved echocardiography, vital signs and biomarkers of patients with chronic heart failure, and reduced the incidence of hyperkalemia, renal dysfunction and other adverse reactions. Further large sample trials are needed in the future to determine the long-term effects of Sacubitril/Valsartan on efficacy and safety in patients with chronic heart failure.

MiRNA-1202 promotes the TGF-ß1-induced proliferation, differentiation and collagen production of cardiac fibroblasts by targeting nNOS.

BACKGROUND: Atrial fibrillation (AF) is a clinically common arrhythmia that affects human health. Myocardial fibrosis serves as an important contributor to AF. Recently, miRNA-1202 have been reported to be up-regulated in AF. However, the role of miRNA-1202 and its mechanism in myocardial fibrosis remain unclear. METHODS: Human cardiac fibroblasts (HCFs) were used to construct a fibrosis model by TGF-ß1 induction. The expression of miR-1202 was measured by qRT-PCR. Cell proliferation was assessed by CCK-8 assays. Protein expression levels were measured by western blot. Collagen accumulation was measured by ELISA. The relationship between miR-1202 and nNOS was investigated by luciferase reporter assays. RESULTS: MiR-1202 expression was obviously increased in HCFs and was both time- and dose-independent. MiR-1202 could increase the proliferation and collagen I, collagen III, and α-SMA levels with or without TGF-ß1. MiR-1202 could also increase TGF-ß1 and p-Smad2/3 protein levels in comparison to the control group. However, they were obviously decreased after inhibitor transfection. MiR-1202 targets nNOS for negative regulation of HCFs fibrosis by decreasing cell differentiation, collagen deposition and the activity of the TGF-ß1/Smad2/3 pathway. Co-transfection of miR-1202 inhibitor and siRNA of nNOS inhibited nNOS protein expression, thereby enhancing the HCFs proliferation. Furthermore, co-transfection of the miR-1202 inhibitor and siRNA of nNOS significantly promoted collagen I, collagen III, TGF-ß1, Smad2/3 and α-SMA protein expression and Smad2/3 protein phosphorylation. These findings suggested that miR-1202 promotes HCFs transformation to a pro-fibrotic phenotype by targeting nNOS through activating the TGF-ß1/Smad2/3 pathway.

hsa-miR-4443 inhibits myocardial fibroblast proliferation by targeting THBS1 to regulate TGF-ß1/α-SMA/collagen signaling in atrial fibrillation.

Fibrosis caused by the increase in extracellular matrix in cardiac fibroblasts plays an important role in the occurrence and development of atrial fibrillation (AF). The aim of this study was to investigate the role of hsa-miR-4443 in AF, human cardiac fibroblast (HCFB) proliferation, and extracellular matrix remodeling. TaqMan Stem-loop miRNA assay was used to measure hsa-miR-4443 expression in patients with persistent AF (n=123) and healthy controls (n=100). Patients with AF were confirmed to have atrial fibrosis by late gadolinium enhancement. At the cellular level, after hsa-miR-4443 mimic and inhibitor were transfected with HCFBs, proliferation, apoptosis, migration, and invasion were analyzed. Lastly, hsa-miR-4443-targeted gene and transforming growth factor (TGF)-ß1/α-SMA/collagen pathway were evaluated by dual-luciferase reporter assay and western blot, respectively. In patients with AF, hsa-miR-4443 decreased significantly and collagen metabolism level increased significantly. Logistic regression analysis showed that low hsa-miR-4443 level was a risk factor of AF (P<0.001). The receiver operating characteristic curve revealed that hsa-miR-4443 was useful for predicting AF (area under the curve: 0.828, sensitivity: 0.71, specificity: 0.78, P<0.001). In HCFBs, hsa-miR-4443 targeted thrombospondin-1 (THBS1) and downregulated TGF-ß1/α-SMA/collagen pathway. The inhibition of hsa-miR-4443 expression promoted HCFB proliferation, migration, invasion, myofibroblast differentiation, and collagen production. The significant reduction of hsa-miR-4443 can be used as a biomarker for AF. hsa-miR-4443 protected AF by targeting THBS1 and regulated TGF-ß1/α-SMA/collagen pathway to inhibit HCFB proliferation and collagen synthesis.

Insight into the effect of pH-adjusted acid on thermodynamic properties and crystallization sequence during evaporative-crystallization process of hydrolyzed urine.

The evaporative-crystallization process (ECP) is a frequently used approach for complete nutrient recovery from human urine, and crystallization sequence is related to the selection of seed and the optimization of crystallization process. In this study, three hydrolyzed urine (HU) samples, which were acidified to an initial pH of 4 with HCl, H2SO4, and H3PO4, were used to recover crystallized products by ECP, their crystallization process and thermodynamic properties during ECP were compared, and the detailed crystallization sequence was analyzed using the PHREEQC-2 simulation. The results showed that the pH-adjusted acid has a significant effect on crystal precipitation, and the new crystal in HCl-4-HU, H2SO4-4-HU, and H3PO4-4-HU first appeared at volume concentration factors (CFV) of 19.61, 9.90, and 9.96, respectively. Furthermore, the simulated crystallization process characteristics of HU by PHREEQC-2 have a good fit with the actual experimental data, and crystallization sequence of HCl-4-HU, H2SO4-4-HU, H3PO4-4-HU during ECP were NH4Cl (CFV from 10.25 to 100) / NaCl (CFV from 71.43 to 100), NH4NaSO4 (CFV from 10.25 to 55.56) / NH4Cl (CFV from 20 to 100) / (NH4)2SO4 (CFV from 40.45 to 100), NH4H2PO4 (CFV from 10.25 to 100) / NaH2PO4 (CFV from38.46 to 55.5) / NaCl (CFV from 45.46 to 100), respectively. The present study clearly reveals the crystallization sequence and thermodynamic properties of nutrient elements in acidified HU, which provides an important theoretical basis for the optimization of crystallized products obtained from HU for future study.

RICK regulates the odontogenic differentiation of dental pulp stem cells through activation of TNF-α via the ERK and not through NF-κB signaling pathway.

Dental pulp stem cells (DPSCs) are capable of both self-renewal and multilineage differentiation, which play a positive role in dentinogenesis. Studies have shown that tumor necrosis factor-α (TNF-α) is involved in the differentiation of DPSCs under pro-inflammatory stimuli, but the mechanism of action of TNF-α is unknown. Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK) is a biomarker of an early inflammatory response that plays a key role in modulating cell differentiation, but the role of RICK in DPSCs is still unclear. In this study, we identified that RICK regulates TNF-α-mediated odontogenic differentiation of DPSCs via the ERK signaling pathway. The expression of the biomarkers of odontogenic differentiation dental matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), biomarkers of odontogenic differentiation, increased in low concentration (1-10 ng/ml) of TNF-α and decreased in high concentration (50-100 ng/ml). Odontogenic differentiation increased over time in the odontogenic differentiation medium. In the presence of 10 ng/L TNF-α, the expression of RICK increased gradually over time, along with odontogenic differentiation. Genetic silencing of RICK expression reduced the expression of odontogenic markers DMP-1 and DSPP. The ERK, but not the NF-κB signaling pathway, was activated during the odontogenic differentiation of DPSCs. ERK signaling modulators decreased when RICK expression was inhibited. PD98059, an ERK inhibitor, blocked the odontogenic differentiation of DPSCs induced by TNF-α. These results provide a further theoretical and experimental basis for the potential use of RICK in targeted therapy for dentin regeneration.

hsa-miR-4443 inhibits myocardial fibroblast proliferation by targeting THBS1 to regulate TGF-ß1/α-SMA/collagen signaling in atrial fibrillation

Fibrosis caused by the increase in extracellular matrix in cardiac fibroblasts plays an important role in the occurrence and development of atrial fibrillation (AF). The aim of this study was to investigate the role of hsa-miR-4443 in AF, human cardiac fibroblast (HCFB) proliferation, and extracellular matrix remodeling. TaqMan Stem-loop miRNA assay was used to measure hsa-miR-4443 expression in patients with persistent AF (n=123) and healthy controls (n=100). Patients with AF were confirmed to have atrial fibrosis by late gadolinium enhancement. At the cellular level, after hsa-miR-4443 mimic and inhibitor were transfected with HCFBs, proliferation, apoptosis, migration, and invasion were analyzed. Lastly, hsa-miR-4443-targeted gene and transforming growth factor (TGF)-β1/α-SMA/collagen pathway were evaluated by dual-luciferase reporter assay and western blot, respectively. In patients with AF, hsa-miR-4443 decreased significantly and collagen metabolism level increased significantly. Logistic regression analysis showed that low hsa-miR-4443 level was a risk factor of AF (P<0.001). The receiver operating characteristic curve revealed that hsa-miR-4443 was useful for predicting AF (area under the curve: 0.828, sensitivity: 0.71, specificity: 0.78, P<0.001). In HCFBs, hsa-miR-4443 targeted thrombospondin-1 (THBS1) and downregulated TGF-β1/α-SMA/collagen pathway. The inhibition of hsa-miR-4443 expression promoted HCFB proliferation, migration, invasion, myofibroblast differentiation, and collagen production. The significant reduction of hsa-miR-4443 can be used as a biomarker for AF. hsa-miR-4443 protected AF by targeting THBS1 and regulated TGF-β1/α-SMA/collagen pathway to inhibit HCFB proliferation and collagen synthesis.

Correction: Technology-Based Interventions in Oral Anticoagulation Management: Meta-Analysis of Randomized Controlled Trials.

[This corrects the article DOI: 10.2196/18386.].

Technology-Based Interventions in Oral Anticoagulation Management: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: An increasing number of patients have received prophylactic or therapeutic oral anticoagulants (OACs) for thromboembolic complications of diseases. The use of OACs is associated with both clinical benefits and risks. Considering the challenges imposed by this class of drugs, as well as the enormous progress made in portable device technology, it is possible that technology-based interventions may improve clinical benefits for patients and optimize anticoagulation management. OBJECTIVE: This study was designed to comprehensively evaluate the role of technology-based interventions in the management of OACs. METHODS: We searched 6 databases-PubMed, EMBASE, Cochrane, Cumulative Index to Nursing and Allied Health Literature, Scopus, and PsycINFO-to retrieve relevant studies published as of November 1, 2019, to evaluate the effect of technology-based interventions on oral anticoagulation management. RevMan (version 5.3; Cochrane) software was used to evaluate and analyze clinical outcomes. The methodological quality of studies was assessed by the Cochrane risk of bias tool. RESULTS: A total of 15 randomized controlled trials (RCTs) were selected for analysis. They reported data for 2218 patients (1110 patients in the intervention groups and 1108 patients in the control groups). A meta-analysis was performed on the effectiveness and safety data reported in the RCTs. Technology-based interventions significantly improved the effectiveness of oral anticoagulation management (mean difference [MD]=6.07; 95% CI 0.84-11.30; I2=72%; P=.02). The safety of oral anticoagulation management was also improved, but the results were not statistically significant. Bleeding events were reduced (major bleeding events MD=1.02; 95% CI 0.78-1.32; I2=0%; P=.90; minor bleeding events MD=1.06, 95% CI 0.77-1.44; I2=41%; P=.73) and thromboembolism events were reduced (MD=0.71; 95% CI 0.49-1.01; I2=0%; P=.06). In general, patients were more satisfied with technology-based interventions, which could also improve their knowledge of anticoagulation management, improve their quality of life, and reduce mortality and hospitalization events. CONCLUSIONS: Using technology to manage OACs can improve the effectiveness and safety of oral anticoagulation management, result in higher patient satisfaction, and allow greater understanding of anticoagulation.

Dysfunction of MiR-148a-NRP1 Functional Axis Suppresses Osteogenic Differentiation of Periodontal Ligament Stem Cells Under Inflammatory Microenvironment.

Periodontitis is a chronic inflammatory disease that can lead to the loss of periodontal bone tissue. The osteogenic potential of periodontal ligament stem cells (PDLSCs) is significantly decreased in periodontitis microenvironment. However, the mechanism is still unclear. We used Porphyromonas gingivalis lipopolysaccharide (LPS) as a stimulator of PDLSCs to mimic the periodontal inflammatory environment. The mineralization capability was restrained in LPS-stimulated PDLSCs, and the level of miR-148a increased, while the level of Neuropilin 1 (NRP1) decreased. Downregulation of miR-148a could reverse the osteogenesis deficiency of PDLSCs under LPS treatment. In addition, the expression of miR-148a in PDLSCs was negatively correlated with the expression of NRP1. Furthermore, overexpression of NRP1 upregulated the osteogenesis ability of LPS-stimulated PDLSCs, while inhibition of NRP1 eliminated the stimulative effect of miR-148a inhibitor on osteogenic differentiation. These data illustrated that the inflammatory environment mimicked by LPS inhibits osteogenesis by upregulation of miR-148a and subsequent downregulation of NRP1. We also found, compared to healthy periodontal tissues, miR-148a level increased, while NRP1 level decreased in periodontitis tissues. These two phenomena also exist in PDLSCs that come from the upper two types of tissues. To summarize, the decline of osteogenic potential of PDLSCs under inflammatory condition of periodontitis is related to miR-148a/NRP1 functional axis. This study may provide a novel strategy in the molecular aspect for the therapy of periodontitis.

Occurrence, distribution, and risk assessment of organophosphate esters in urban street dust in the central province of Henan, China.

In this study, nine OPEs were measured in 60 street dust samples collected from the central province of Henan, China. The total concentrations of OPEs (∑9OPEs) in street dust range from 2.77 to 505 µg/kg (median 59.3 µg/kg). Chlorinated OPEs are dominant in street dust with median concentration of 33.5 µg/kg, followed by aryl OPEs (median 9.05 µg/kg), and alkyl OPEs (median 6.19 µg/kg). No significant correlations are found between ∑9OPEs and parameters, such as population (p = 0.931), population density (p = 0.602), car ownership (p = 0.618), and gross domestic product (p = 0.863). Principal component analysis (PCA) result reveals that road traffic could be a major source of OPEs in street dust because of their extensive use in various vehicles. The total average (median) and high-level exposure (95th percentile) of OPEs are 1.01 × 10-2, 7.17 × 10-2 ng/kg bw/d for adults and 6.03 × 10-2, 0.43 ng/kg bw/d for children, respectively. Hazard quotient (HQ) values are 5-6 orders of magnitude lower than the acceptable risk level (HQ < 0.1), indicating there is still a low risk to local residents at current levels.

Organophosphate flame retardants in total suspended particulates from an urban area of zhengzhou, China: Temporal variations, potential affecting factors, and health risk assessment.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in industry and daily life, but the partition of OPEs to particles is still unclear because of the wide range of their physicochemical properties. In this study, six target OPEs with different vapor pressures (log PL) were measured from 30 total suspended particulate (TSP) samples collected from an urban area of Zhengzhou from June to November in 2018. The total concentration of OPEs ranged from 0.30 to 3.46 ng/m3, with average concentration of 1.04 ng/m3. Tris (chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCPP), and tributyl phosphate (TnBP) were most abundant in TSP, accounting for approximately 86.0% to the total OPEs. The temporal variations showed a specific trend that OPE concentrations in TSP were much higher in autumn than those of summer. Significant positive correlations were observed between TSP concentration in air and the total concentration of OPEs in TSP, with r up to 0.596. Particle concentrations caused major changes on OPE concentrations in TSP with octanol-air partition coefficient (log KOA) between 7.7 and 10 but had no significant influence on the OPEs with log KOA higher than 12. Temperature had significant influence on the total and individual OPEs with high vapor pressures (log PL > -4.0), indicating that log KOA and log PL had significant influence on the OPE concentrations in TSP and may be one of the key factors on their temporal variations. Temperature had significant influence on OPE concentrations in TSP due to the strong temperature dependency of log KOA and log PL. No significant relationships were found between the wind speed and OPE concentrations in TSP, suggesting that OPEs detected in TSP might be emitted from the local sources. The hazards quotient (HQ) values were 6-8 orders of magnitude lower than 1, indicating that there was a low risk to local residents from the exposure to OPEs in TSP. This study preliminarily illuminates the potential affecting factors on the temporal variations of OPEs in TSP. It would be helpful for investigating the gas-particle partitioning behaviors and human health risks of OPEs in air.

The Forkhead Box C1, a Novel Negative Regulator of Osteogenesis, Plays a Crucial Role in Odontogenic Differentiation of Dental Pulp Stem Cells.

The forkhead box C1 (Foxc1) protein, a member of the forkhead/winged helix transcription factor family, is required in stem cell developmental processes. Recently, multiple studies have indicated the crucial role of Foxc1 in mesenchymal stem cell differentiation, but the precise effects and mechanisms on dental pulp stem cells (DPSCs) remain unclear. In this study, we evaluate the role of Foxc1 on the odontogenic differentiation and proliferation of DPSCs. Our results show that Foxc1 decreases time dependently in odontogenic differentiation of DPSCs. Meanwhile, overexpression of Foxc1 could significantly inhibit the mineralization of DPSCs and the expression of odontogenic-related genes, such as runt-related transcription factor 2 (Runx2), dentin sialophosphoprote (DSPP), and dentin matrix acidic phosphoprotein 1 (DMP-1). Foxc1 overexpression does not significantly alter the proliferation of DPSCs. In addition, Foxc1 reduces the expression of p-Smad1/5, an important modulator of bone morphogenetic protein (BMP)/Smad signaling pathway, inhibiting BMP/Smad signaling pathway. In conclusion, our data demonstrated that Foxc1 inhibits odontogenic differentiation of DPSCs and odontogenic-related gene expression through the BMP/Smad signaling pathway which may be useful for the dental regeneration and repair.

MiR-21/STAT3 Signal Is Involved in Odontoblast Differentiation of Human Dental Pulp Stem Cells Mediated by TNF-α.

Dental pulp stem cells (DPSCs), as one type of mesenchymal stem cells (MSCs), have the capability of self-renewal and multipotency to differentiate into several cell lineages, including osteogenesis, odontoblasts, chondrogenesis, neurogenesis, and adipogenesis. It has found that tumor necrosis factor-α (TNF-α) can promote osteogenic differentiation of human DPSCs in our previous studies. Other experimentation revealed that signal transducer and activator of transcription 3 (STAT3) underwent a rapid activation both in osteogenesis and inflammation microenvironment of MSCs in vitro. MicroRNAs (miRNAs or miRs) have been proved in previous studies to regulate MSCs differentiation in vitro. In this study, we identified miR-21 as a key miRNA contributed the functional axis of odontoblast differentiation induced by STAT3. It is observed that the expression of miR-21 and STAT3 increased gradually in low concentration (1-10 ng/mL) of TNF-α, while they were suppressed in high concentration (50-100 ng/mL). The upregulation of miR-21 may facilitate the odontoblast differentiation of DPSCs coordinating with STAT3. SiSTAT3 or treated by the inhibitor of STAT3, cucurbitacin I (Cuc I), significantly increased primary miR-21 expression along with decreased mature miR-21 expression. Meanwhile, the inhibition of miR-21 (anti-miR-21) decreased the activation of STAT3 as well as suppressed the marker proteins of odontoblast differentiation. The results revealed a new function of miR-21, suggesting that miR-21/STAT3 signal may act as a modulator within a complex network of factors to regulate odontoblast differentiation of human DPSCs. It may provide a novel therapeutic strategy to regulate the odontoblast differentiation of DPSCs.