Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension.

BACKGROUND: Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy (HE). It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt (TIPS) is related to postoperative HE. AIM: To investigate the relationship between spleen volume and the occurrence of HE. METHODS: This study included 135 patients with liver cirrhosis who underwent TIPS, and liver and spleen volumes were elevated upon computed tomography imaging. The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes. Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE (OHE). Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk. RESULTS: The results showed that 37 (27.2%) of 135 patients experienced OHE during a 1-year follow-up period. Compared with preoperative spleen volume (901.30 ± 471.90 cm3), there was a significant decrease in spleen volume after TIPS (697.60 ± 281.0 cm3) in OHE patients. As the severity of OHE increased, the spleen volume significantly decreased (P < 0.05). Compared with patients with a spleen volume ≥ 782.4 cm3, those with a spleen volume < 782.4 cm3 had a higher incidence of HE (P < 0.05). Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE (hazard ratio = 0.494, P < 0.05). Restricted cubic spline model showed that with an increasing spleen volume, OHE risk showed an initial increase and then decrease (P < 0.05). CONCLUSION: Spleen volume is related to the occurrence of OHE after TIPS. Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

A preliminary study on calcifying nanoparticles in dental plaque: Isolation, characterization, and potential mineralization mechanism.

OBJECTIVES: Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease. MATERIAL AND METHODS: Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). RESULTS: The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate. CONCLUSION: CNPs were found in periodontitis-related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.

HA2-FimA DNA Vaccine Treats Experimental Periodontitis.

PURPOSE: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. MATERIALS AND METHODS: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2-FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). RESULTS: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). Micro-CT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). CONCLUSION: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.

Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway.

Fluoride (F) and sulfur dioxide (SO2) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO2 can cause abnormal enamel mineralization. Ameloblastin (AMBN) plays a crucial role in the process of enamel mineralization. However, the process by which simultaneous exposure to F and SO2 influences enamel formation by regulating AMBN expression still needs to be understood. This study aimed to establish in vivo and in vitro models of F-SO2 Co-exposure and investigate the relationship between AMBN and abnormal enamel mineralization. By overexpressing/knocking out the Fibroblast Growth Factor 9 (FGF9) gene, we investigated the impact of FGF9-mediated Mitogen-Activated Protein Kinase (MAPK) signaling on AMBN synthesis to elucidate the mechanism underlying the induction of abnormal enamel mineralization by F-SO2 Co-exposure in rats. The results showed that F-SO2 exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO2, gradual increases in the protein expression of FGF9 and phosphorylated p38 mitogen-activated protein kinase (p-P38) were observed. Conversely, the protein levels of AMBN, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) were decreased. AMBN expression was significantly correlated with FGF9, p-ERK, and p-JNK expression in ameloblasts. Interestingly, FGF9 overexpression reduced the levels of p-ERK and p-JNK, worsening the inhibitory effect of F-SO2 on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO2-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO2-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways.

Transcriptome Sequencing of Gingival Tissues from Impacted Third Molars Patients Reveals the Alterations of Gene Expression.

OBJECTIVE: The removal of impacted third molars by surgery may occur with a series of complications, whereas limited information about the postoperative pathogenesis is available. The objective of this study is to identify changes in gene expression after flap surgical removal of impacted third molars and provide potential information to reduce postoperative complications. METHODS: The gingival tissues of twenty patients with flap surgical removal of impacted third molars and twenty healthy volunteers were collected for gene expression testing. The collected gingival tissues were used RNA sequencing technology and quantitative real-time PCR validation was performed. DEG was mapped to protein databases such as GO and KEGG for functional annotation and, based on annotation information, for mining of differential expression genes in patients with mpacted third molars. RESULTS: A total of 555 genes were differentially expressed. Among the top up-regulated genes, HLA-DRB4, CCL20, and CXCL8 were strongly associated with immune response and signal transduction. Among the top down-regulated genes, SPRR2B, CLDN17, LCE3D and LCE3E were related to keratinocyte differentiation, IFITM5, and BGLAP were related to bone mineralization, UGT2B17 is associated with susceptibility to osteoporosis. KEGG results showed that the DEGs were related to multiple disease-related pathways. CONCLUSION: This first transcriptome analysis of gingival tissues from patients with surgical removal of impacted third molars provides new insights into postoperative genetic changes. The results may establish a basis for future research on minimizing the incidence of complications after flap-treated third molars.

Influence of myoglobin on the antibacterial activity of carvacrol and the binding mechanism between the two compounds.

BACKGROUND: Myoglobin (MB), a pigmentation protein, can adversely affect the antibacterial activity of carvacrol (CAR) and weaken its bacteriostasis effect. This study aimed to clarify the influence of MB on the antibacterial activity of CAR and ascertain the mechanism involved in the observed influence, especially the interaction between the two compounds. RESULTS: Microbiological analysis indicated that the presence of MB significantly suppressed the antibacterial activity of CAR against Listeria monocytogenes. Ultraviolet-visible spectrometry and fluorescence spectroscopic analysis confirmed the interaction between CAR and MB. The stoichiometric number was determined as ~0.7 via double logarithmic Stern-Volmer equation analysis, while thermodynamic analysis showed that the conjugation of the two compounds occurred as an exothermal reaction (ΔH° = -32.3 ± 11.4 kJ mol-1 and ΔS° = -75 J mol-1 K-1 ). Circular dichroism, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy showed hydrogen bonding in the carvacrol-myoglobin complex (CAR-MB). Molecular docking analysis confirmed that amino acid residues, including GLY80 and HIS82, were most likely to form hydrogen bonds with CAR, while hydrogen bonds represented the main driving force for CAR-MB formation. CONCLUSION: CAR antibacterial activity was significantly inhibited by the presence of MB in the environment due to the notable reduction in the effective concentration of CAR caused by CAR-MB formation. © 2023 Society of Chemical Industry.

MiR-1a-3p Inhibits Apoptosis in Fluoride-exposed LS8 Cells by Targeting Map3k1.

Dental fluorosis is a common chemical disease. It is currently unclear how fluorosis occurs at the molecular level. We used miRNA-seq to look at the differences between miRNAs in the cell line of ameloblasts LS8 that had been treated with 3.2 mmol/L NaF. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. miR-1a-3p levels were significantly lower in mouse LS8 cells treated with 3.2 mmol/L NaF, and miR-1a-3p-targeted genes were significantly enriched in the MAPK pathway. LS8 cells were divided into four groups: control, NaF, NaF+miR-1a-3p mimics, and NaF+miR-1a-3p mimics normal control groups. Cellular morphology was observed by an inverted microscope, and the proliferation activity of LS8 cells was assessed by Cell Counting Kit-8 (CCK-8). Using the real-time quantitative polymerase chain reaction (RT-qPCR), transcription levels of miR-1a-3p and Map3k1 were detected. The expressions of Bax, Bcl-2, Map3k1, p38MAPK, ERK1/2, p-p38MAPK, and p-ERK1/2 were measured by Western blot. After bioinformatics analysis, we used a luciferase reporter assay (LRA) to validate the target of miR-1a-3p, showing that miR-1a-3p could inhibit apoptosis while increasing proliferation in fluoride-exposed LS8 cells. Generally, miR-1a-3p might directly inhibit Map3k1, reduce MAPK signal pathway activation, and promote phosphorylation. Thus, our findings revealed that the interaction of miR-1a-3p with its target gene Map3k1 and MAPK signal pathway might decrease the apoptosis of LS8 cells treated with 3.2 mmol/L NaF.

Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model.

Background/purpose: Epigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methods: Periodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. Results: EGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1ß, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. Conclusion: These results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

The role of FGF9-mediated TGF-ß1/Smad signaling in enamel hypoplasia induced by exposure to fluoride and SO2 in rats.

Many geographical areas of the world are polluted by both fluoride and sulfur dioxide (SO2). However, the effects of simultaneous exposure to fluoride and SO2 on teeth are unknown. Fibroblast growth factor-9 (FGF9) and transforming growth factor-ß1 (TGF-ß1) are key signaling molecules in enamel development. The purpose of the study was to explore the effects of co-exposure to fluoride and sulfur dioxide on enamel and to investigate the role and mechanism of FGF9 and TGF-ß1. First, sodium fluoride (NaF) and SO2 derivatives were used to construct rat models and evaluate the enamel development of rats. Then, TGF-ß1 (cytokine) treatment, SIS3 (inhibitor) treatment and FGF9 gene knockdown were used to explore the mechanism of enamel damage in vitro. The results showed that enamel column crystals in the exposed group were characterized by enamel hypoplasia, as indicated by alterations such as disarrangement of enamel column crystals, space widening and breakage. Ameloblasts also showed pathological changes such as ribosome loss, mitochondrial swelling, nuclear fragmentation and chromatin aggregation. The protein expression of FGF9 was higher and the protein expression of AMBN, TGF-ß1 and p-Smad2/3 protein was lower in the groups treated with fluoride and SO2 individually or in combination compared with the control group. Further studies showed that TGF-ß1 significantly upregulated p-Smad2/3 and AMBN protein expression and reduced the inhibitory effects of fluoride and SO2; furthermore, SISI blocked the effect of TGF-ß1. In addition, knockdown of FGF9 upregulated TGF-ß1 protein expression, further activated Smad2/3 phosphorylation, eliminated the inhibitory effects of fluoride and SO2, and increased the protein expression of AMBN. In brief, the study confirms that co-exposure to fluoride and SO2 can result in enamel hypoplasia in rats and indicates that the underlying mechanism may be closely related to the effect of FGF9 on enamel matrix protein secretion through inhibition of the TGF-ß1/Smad signaling pathway.

A novel edible colorant lake prepared with CaCO3 and Monascus pigments: Lake characterization and mechanism study.

Monascus pigments (MPs) were adsorbed using calcium carbonate to produce CaCO3-MPs lakes. The fundamental properties and formation mechanism of the lakes were investigated. Results indicated that CaCO3 displayed a high enough affinity for the MPs to form colorant lakes, while the MPs tended to transform the CaCO3 crystals from calcite to vaterite. The adsorption of MPs by CaCO3 followed the Freundlich isothermal model with n value higher than 1, confirming it as physical adsorption. The ΔG0 (-29 to ∼-33 kJ/mol) and ΔH0(30-55 kJ/mol) indicated that lake formation was a spontaneous and endothermic process. UV/Vis spectroscopic analysis verified the complex formation between Ca2+ and MPs via physical bonding, suggesting a possible attraction between the Ca2+ and glutamate residues of the MPs. EDS showed that the MPs were trapped inside the particles. FTIR spectroscopy and XPS further confirmed that the physical bonding was the primary driving force behind the lake formation.

Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents.

Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative A17 (namely tumulosic acid, also found in Poria cocos), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC50 values of 7.36 ± 0.98 and 2.50 ± 0.15 µM, respectively. Further pharmacological analysis demonstrated that A17 induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of A17 on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition, A17 regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that A17 possesses great potential as an anticancer agent.

Sulphur dioxide and fluoride co-exposure cause enamel damage by disrupting the Cl-/HCO3- ion transport.

OBJECTIVE: Although there is growing evidence linking the exposure to sulphur dioxide (SO2) and fluoride to human diseases, there is little data on the co-exposure of SO2 and fluoride. Moreover, literature on SO2 and fluoride co-exposure to enamel damage is insufficient. In this work, we concentrate on the concurrent environmental issues of excessive SO2 and fluoride in several coal-consuming regions. METHOD: To identify the toxicity of SO2 and fluoride exposure either separately or together, we used both ICR mice and LS8 cells, and factorial design was employed to assess the type of potential combined action. RESULT: In this study, co-exposure to SO2 and fluoride exacerbated enamel damage, resulting in more severe enamel defects of incisor and the damage occurred earlier. Cl-/HCO3- exchanger expression is increased by SO2 and fluoride in mouse incisor. Consistent with in vivo results, co-exposure of SO2 and fluoride decreased pHi and increased [Cl-]i level by increasing the expression of the Cl-/HCO3- exchanger in LS8 cells. Furthermore, SO2 and F may increase merlin protein expression, and merlin deficiency causes AE2 expression to decrease in vitro. CONCLUSION: Overall, these results indicate that co-exposure to SO2 and fluoride may result in more toxicity both in vitro and in vivo than a single exposure to SO2 and fluoride, suggesting that residents in areas contaminated with SO2 and fluoride may be more likely to suffer enamel damage.

N6­methyladenosine­induced long non­coding RNA PVT1 regulates the miR­27b­3p/BLM axis to promote prostate cancer progression.

Prostate cancer (PCa) is one of the most fundamental causes of cancer­related mortality and morbidity among males. However, the underlying mechanisms have not yet been fully clarified. The present study aimed to investigate the effects of plasmacytoma variant translocation 1 (PVT1) on the malignant behaviors of PCa cells and to explore the possible molecular mechanisms involved. The expression levels of PVT1 and microRNA (miRNA/miR)­27b­3p in PCa tissues and cell lines were measured using reverse­transcritpion­quantitative polymerase chain reaction. Methyltransferase 3 (METTL3)­mediated PVT1 N6­methyladenosine (m6A) modifications were detected using RNA immunoprecipitation (RIP) and RNA pull­down assays. Bioinformatics analysis was used to predict the interactions of miR­27b­3p with PVT1 and bloom syndrome protein (BLM), and these interactions were validated using RIP, dual­luciferase reporter and biotin pull­down assays. The functional importance of miR­27b­3p, PVT1 and BLM within PCa cells was assessed through the in vitro utilization of Cell Counting Kit­8, Transwell, wound healing and colony formation assays, and the in vivo use of a mouse xenograft model. The results revealed the high expression level of PVT1 in PCa tissues and cells, and epigenetic analyses revealed the upregulation of PVT1 expression following METTL3­mediated m6A modification. PVT1 overexpression induced PCa cells to become more proliferative, migratory and invasive, whereas PVT1 knockdown led to the opposite phenotype. Furthermore, miR­27b­3p was found to target both PVT1 and BLM, and PVT1 functioned to sequester miR­27b­3p within cells, thereby indirectly promoting the BLM expression level. BLM overexpression reversed the adverse effects of PVT1 knockdown on the migratory, proliferative and invasive capabilities of PCa cells in vitro and in vivo. The overexpression of PVT1 contributed to the aggressive phenotype of PCa cells by regulating the miR­27b­3p/BLM axis. On the whole, the findings of the present study may provide novel potential targets for the treatment of PCa.

Sodium Fluoride and Sulfur Dioxide Derivatives Induce TGF-ß1-Mediated NBCe1 Downregulation Causing Acid-Base Disorder of LS8 Cells.

The aim of the present work was to assess whether the combination of sodium fluoride (NaF) and sulfur dioxide derivatives (SO2 derivatives) affects the expression of the electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4), triggering an acid-base imbalance during enamel development, leading to enamel damage. LS8 cells was taken as the research objects and fluorescent probes, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and factorial analysis were used to clarify the nature of the fluoro-sulfur interaction and the potential signaling pathway involved in the regulation of NBCe1. The results showed that exposure to fluoride or SO2 derivatives resulted in an acid-base imbalance, and these changes were accompanied by inhibited expression of NBCe1 and TGF-ß1; these effects were more significant after fluoride exposure as compared to exposure to SO2 derivatives. Interestingly, in most cases, the toxic effects during combined exposure were significantly reduced compared to the effects observed with fluoride or sulfur dioxide derivatives alone. The results also indicated that activation of TGF-ß1 signaling significantly upregulated the expression of NBCe1, and this effect was suppressed after the Smad, ERK, and JNK signals were blocked. Furthermore, fluoride and SO2 derivative-dependent NBCe1 regulation was found to require TGF-ß1. In conclusion, this study indicates that the combined effect of fluorine and sulfur on LS8 cells is mainly antagonistic. TGF-ß1 may regulate NBCe1 and may participate in the occurrence of dental fluorosis through the classic TGF-ß1/Smad pathway and the unconventional ERK and JNK pathways.

Geniposide inhibits cell proliferation and migration in human oral squamous carcinoma cells via AMPK and JNK signaling pathways.

Iridoids are a special class of cyclopentanoid monoterpenes, which exhibit a wide range of biological effects. The present study aimed to investigate the potential effects of three iridoids genipin, geniposide and geniposidic acid on three human oral squamous cell carcinoma (OSCC) cell lines HSC-2, SCC-9 and A253 in addition to studying the possible underlying mechanisms. Cell viability assay revealed that geniposide treatment significantly suppressed the proliferation of all three cancer cell lines. In addition, geniposide induced SCC-9 cell cycle arrest at the G2/M phase (flow cytometry) through downregulation of cyclin-dependent kinase 2 and Cyclin A2 expression (western blot analysis), whilst also inducing cell apoptosis (flow cytometry and acridine orange/ethidium bromide staining) by dissipating the mitochondrial membrane potential (flow cytometry), and upregulating the expression of cleaved caspase-3 and cleaved poly-ADP ribose polymerase (western blot analysis). A wound-healing assay indicated that geniposide impaired SCC-9 cell migration by increasing the expression of E-cadherin (western blot analysis), whilst suppressing the expression of MMP-2 (western blot analysis). Western blot analysis also demonstrated that geniposide induced autophagy in SCC-9 cells by upregulating the expression of Beclin-1 and light chain 3-II. Mechanistically, geniposide activated the 5'-AMP-activated protein kinase signaling pathway and inhibited the JNK signaling pathway in SCC-9 cells (western blot analysis). The present results indicated that geniposide is able to inhibit the proliferation and migration of the tongue squamous carcinoma cell line SCC-9, suggesting a potential strategy for OSCC treatment.

Sulphur dioxide and fluoride co-exposure induce incisor hypomineralization and amelogenin upregulation via YAP/RUNX2 signaling pathway.

Sulphur dioxide (SO2) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO2 and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO2 and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO2 and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO2 and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO2 and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO2 and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO2 and fluoride may have an increased risk of developing enamel damage.

Pharmacological profiles and therapeutic applications of pachymic acid (Review).

Poria cocos is a saprophytic fungus that grows in diverse species of Pinus. Its sclerotium, called fu-ling or hoelen, has been used in various traditional Chinese medicines and health foods for thousands of years, and in several modern proprietary traditional Chinese medicinal products. It has extensive clinical indications, including sedative, diuretic, and tonic effects. Pachymic acid (PA) is the main lanostane-type triterpenoid in Poria cocos. Evidence suggests that PA has various biological properties such as cytotoxic, anti-inflammatory, antihyperglycemic, antiviral, antibacterial, sedative-hypnotic, and anti-ischemia/reperfusion activities. Although considerable advancements have been made, some fundamental and intricate issues remain unclear, such as the underlying mechanisms of PA. The present study aimed to summarize the biological properties and therapeutic potential of PA. The biosynthetic, pharmacokinetic, and metabolic pathways of PA, and its underlying mechanisms were also comprehensively summarized.

Effect of Eucommia water extract on gingivitis and periodontitis in experimental rats.

Herein, we evaluated the potential therapeutic effects of water extracts from Eucommia on periodontitis in experimental rats. We ligated the maxillary second molars of Sprague-Dawley(SD) rats with 4.0 silk threads and locally smeared Porphyromonas gingivalis(P. gingivalis) to induce gingivitis and periodontitis.After the model was successfully established, we exposed the rats to Eucommia water extracts through topical smearing and intragastric administration and evaluated the therapeutic effect of the extracts on gingivitis (for a 2 week treatment period) and periodontitis (over 4 weeks). We analyzed histopathological sections of the periodontal tissue and quantified the alveolar bone resorption levels, molecules related to periodontal oxidative stress, and periodontal inflammatory factors to assess the feasibility of Eucommia in treating gingivitis and periodontitis. We found that damage to the periodontal tissue was reduced after treatment with extracts,indicating that Eucommia has a positive effect in treating gingivitis and periodontitis in experimental rats. These findings are expected to provide the foothold for future research on secondary metabolites derived from Eucommia and guide the development of novel approaches for preventing and treating periodontal disease.

BTBD7 accelerates the epithelial-mesenchymal transition, proliferation and invasion of prostate cancer cells.

PURPOSE: To investigate the potential function of BTBD7 in prostate cancer (PCa) development and the underlying molecular mechanism. METHODS: Serum levels of BTBD7 in PCa patients were examined by qRT-PCR. Regulatory effects of BTBD7 on viability and invasiveness were detected by CCK-8 and Transwell assay, respectively. Moreover, Western blot analysis was conducted to examine protein levels of epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) in PCa cells intervened by BTBD7. RESULTS: Serum level of BTBD7 was increased in PCa patients, especially those with Gleason score ≥8 or TNM staging Ⅲ+Ⅳ. Knockdown of BTBD7 attenuated the viability and invasiveness of PCa cells, which upregulated E-cadherin and downregulated N-cadherin. CONCLUSION: Serum level of BTBD7 increases in PCa patients. It accelerates PCa development by triggering proliferative and invasive potentials, as well as EMT.