ABSTRACT
Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34ßE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Male , Humans , Female , Aged , Middle Aged , Esophageal Neoplasms/genetics , Phosphatidylinositol 3-Kinases , Cell Differentiation , Carcinoma, Squamous Cell/geneticsABSTRACT
Objective: To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis. Methods: The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS. Results: Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05). Conclusion: Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , alpha-Fetoproteins , Retrospective StudiesABSTRACT
Objective: To study the impact of regional positive lymph node ratio (LNR) on prognosis of patients with gallbladder carcinoma. Methods: The clinicopathological and survival data of 53 patients with gallbladder carcinoma who underwent radical resection with regional lymph node metastasis in Ningbo University Affiliated Lihuili Hospital from May 2012 to December 2020 were collected, and receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value of LNR for predicting postoperative survival status in patients with gallbladder carcinoma. According to the critical value, the patients were divided into low LNR group and high LNR group. The clinicopathological features and prognosis of the two groups were compared. Log rank test was used for univariate analysis of prognostic factors in patients with gallbladder carcinoma, and Cox proportional hazards model was used for multivariate analysis. Results: A total of 417 regional lymph nodes were dissected in 53 patients, of which 144 lymph nodes were positive, with a positive rate of 34.5%. The optimal cut-off value of LNR for predicting postoperative survival status of patients with gallbladder carcinoma was 0.33. According to this cut-off value, patients were divided into low LNR group (LNR≤0.33, 28 cases) and high LNR group (LNR>0.33, 25 cases). The recurrence rates were 64.3% (18/28) and 88.0 % (22/25) in low LNR group and high LNR group, respectively. The median recurrence-free survival (RFS) was 8 and 7 months, respectively (P=0.032). In the low LNR group, the 1-, 3-, and 5-year survival rates were 56.2%, 38.4%, and 32.0%, respectively, and the median overall survival (OS) was 16 months. In the high LNR group, the 1-, 3-, and 5-year survival rates were 37.9%, 5.4%, and 0, respectively, and the median OS was 9 months. The postoperative survival rate of patients in the low LNR group was better than that in the high LNR group (P=0.008). Univariate analysis showed that LNR was even associated with RFS and OS in patients with gallbladder carcinoma (P<0.05). Multivariate analysis showed that LNR>0.33 was an independent risk factor for postoperative RFS (HR=1.977, 95% CI: 1.045-3.740), but not for OS (HR=1.561, 95% CI: 0.685-3.553). Conclusion: On the basis of clearing a sufficient number of regional lymph nodes, patients with gallbladder carcinoma with regional LNR>0.33 are more likely to relapse after operation, but the predictive value of LNR>0.33 OS is insufficient.
Subject(s)
Gallbladder Neoplasms , Lymph Node Ratio , Humans , Gallbladder Neoplasms/pathology , Lymph Node Excision , Lymphatic Metastasis/pathology , Neoplasm Staging , Retrospective Studies , Lymph Nodes/pathology , PrognosisABSTRACT
We report muon spin rotation and magnetic susceptibility experiments on in-plane stress effects on the static spin-stripe order and superconductivity in the cuprate system La_{2-x}Ba_{x}CuO_{4} with x=0.115. An extremely low uniaxial stress of â¼0.1 GPa induces a substantial decrease in the magnetic volume fraction and a dramatic rise in the onset of 3D superconductivity, from â¼10 to 32 K; however, the onset of at-least-2D superconductivity is much less sensitive to stress. These results show not only that large-volume-fraction spin-stripe order is anticorrelated with 3D superconducting coherence but also that these states are energetically very finely balanced. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. These results strongly suggest a similar pairing mechanism for spin-stripe order and the spatially modulated 2D and uniform 3D superconducting orders, imposing an important constraint on theoretical models.
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Fruit juice addition can influence the physiochemical and sensory properties of fermented milk. Effects of adding strawberry juice (15% vol/vol) pre- or postfermentation on particle size, rheology properties, volatile flavor profile, and microstructure of fermented goat milk were investigated. Samples with juice added prefermentation showed larger reinforcement in particle size, apparent viscosity, and storage and loss moduli than samples with juice added postfermentation. Compared with the control, all samples showed improved fruit aroma and reduced goaty flavor; this effect was more remarkable in samples in which juice was added before fermentation. Fermented goat milk with strawberry juice added prefermentation showed the highest levels of 1-hexanol and 2-hexen-1-ol (26.16 and 22.03%, respectively) and the lowest percentage of octanoic acid (2.47%), which are mainly responsible for fruit and goaty flavor, respectively. Microstructure analysis showed that samples with juice added prefermentation had a compact protein network. Results indicated that addition of strawberry juice before fermentation may be a good technology for developing a stirred strawberry fermented goat milk.
Subject(s)
Food Additives , Fragaria , Fruit and Vegetable Juices , Milk/chemistry , Animals , Fermentation , Goats , TasteABSTRACT
Soybean lecithin is often used as a surfactant in food formulation. The aim of this study was to investigate the interactions between soybean lecithin (SL, 0-3%, wt/vol) and whey protein (WP, 10%, wt/vol) or polymerized whey protein (PWP, 10%, wt/vol) induced by heating WP solutions at 85°C for 0 to 20 min at pH 7.0. The samples were evaluated for zeta potential, particle size, morphology, rheological properties, thermal properties, secondary structure, and surface hydrophobicity. Zeta potential of WP increased linearly as SL level increased from 0 to 3%, whereas that of PWP changed with plateau at SL level of 1%, which may be due to the aggregation of SL. The addition of SL increased the particle size and apparent viscosity of both WP and PWP. All the samples exhibited different morphology depending on SL level and heating time according to transmission electron microscopy images. Whey protein showed obviously decreased gelation time and increased storage modulus in the presence of SL. Differential scanning calorimetry curves confirmed the effects of SL on the thermal properties of both WP and PWP. Circular dichroism spectra indicated that SL had effects on the secondary structure of both WP and PWP. The changes in surface hydrophobicity indicated the hydrophobic interactions between WP/PWP and SL. Data indicate that the physicochemical and functional properties of WP and PWP can be altered by adding soybean lecithin.
Subject(s)
Glycine max/chemistry , Lecithins/chemistry , Whey Proteins/chemistry , Animals , Chemical Phenomena , Gels , Hydrophobic and Hydrophilic Interactions , Microscopy, Electron, Transmission , Particle Size , Polymerization , Rheology , Surface-Active Agents , Thermodynamics , ViscosityABSTRACT
Gamma radiation has been used in food processing for many years, though it has certain effects on food components. Whey protein solutions (10%/30%, wt/vol) were treated with gamma radiation at various dosages (10-25 kGy) and evaluated for microbial changes in the solutions and physicochemical and structural changes of whey proteins. Whey protein solutions after gamma radiation showed substantially lower populations of all viable microorganisms than those of controls. The 10% whey protein solution treated at radiation of 20 or 25 kGy remained sterile for up to 4 wk at room temperature. Gamma radiation increased viscosity and turbidity and decreased soluble nitrogen of whey protein solutions compared to nonradiated control samples regardless of radiation dosage. Nonreducing sodium dodecyl sulfate-PAGE suggested that whey proteins under gamma radiation treatment formed aggregates with high molecular weights. Reducing sodium dodecyl sulfate-PAGE showed that disulfide bonds played a role in gamma radiation-induced whey protein cross-linking. Scanning and transmission electron microscopy micrographs exhibited large aggregates of whey proteins after gamma radiation treatment. Results suggested that gamma radiation could be applied to whey protein solution for purposes of reducing microbial counts and cross-linking protein molecules.
Subject(s)
Bacteria/radiation effects , Whey Proteins/radiation effects , Whey/microbiology , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Cattle , Electrophoresis, Polyacrylamide Gel , Food Irradiation , Gamma Rays , Microscopy, Electron, Transmission , Models, Biological , Viscosity , Whey/radiation effects , Whey Proteins/chemistryABSTRACT
OBJECTIVE: We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, during a 13-week treatment period in Chinese patients with chronic pain due to osteoarthritis (OA). DESIGN: Patients were at least 40 years old (male or female) who met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee or hip. The primary efficacy measure in this phase 3, randomized, double-blind, placebo-controlled clinical trial was assessment of pain severity by the Brief Pain Inventory (BPI) 24-h Average Pain rating. The clinical trial was conducted at 17 study centers. Statistical approaches included mixed-effects model repeated measures and analysis of covariance. A Fisher exact test was applied to categorical variables. RESULTS: Of 407 patients randomized (duloxetine: N = 205; placebo: N = 202), 166 (81.0%) patients from the duloxetine group and 176 (87.1%) patients from the placebo group completed the 13-week treatment phase. The majority (76.4%) of patients was female; mean age was 60.5 years. Duloxetine-treated patients reported significant pain reduction, compared with placebo treatment, on the BPI 24-h Average Pain rating (least-squares mean (LS Mean) change from baseline to endpoint [95% confidence interval (CI)], duloxetine: -2.23; placebo: -1.73; difference = -0.50 [-0.80, -0.20]; P = 0.001). The incidence of discontinuations due to adverse events was 9.0% in duloxetine-treated patients and 4.5% in placebo-treated patients (P = 0.109). CONCLUSIONS: This study demonstrated the efficacy of duloxetine in Chinese patients with chronic pain due to OA. The safety profile of duloxetine observed in this study was consistent with that in previous duloxetine trials. This trial is registered with ClinicalTrials.gov (NCT01931475).
Subject(s)
Analgesics/therapeutic use , Chronic Pain/drug therapy , Duloxetine Hydrochloride/therapeutic use , Osteoarthritis, Hip/drug therapy , Osteoarthritis, Knee/drug therapy , Aged , Asian People , Chronic Pain/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Osteoarthritis, Hip/complications , Osteoarthritis, Knee/complications , Treatment OutcomeABSTRACT
BACKGROUND: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. METHODS: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. RESULTS: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: -2.40, placebo: -1.97; LS mean change difference (95% confidence interval) = -0.43 (-0.82, -0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). CONCLUSIONS: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials.
Subject(s)
Analgesics/therapeutic use , Diabetic Neuropathies/drug therapy , Duloxetine Hydrochloride/therapeutic use , Neuralgia/drug therapy , Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use , Adult , Aged , China , Double-Blind Method , Female , Humans , Male , Middle Aged , Pain Measurement , United StatesABSTRACT
With ellipsometry, x-ray diffraction, and resistance measurements we investigated the electric-field effect on the confined electrons at the LaAlO3/SrTiO3 interface. We obtained evidence that the localization of the electrons at negative gate voltage is induced, or at least enhanced, by a polar phase transition in SrTiO3 which strongly reduces the lattice polarizability and the subsequent screening. In particular, we show that the charge localization and the polar order of SrTiO3 both develop below â¼50 K and exhibit similar, unipolar hysteresis loops as a function of the gate voltage.
ABSTRACT
Elucidation of the evolutionary processes that constrain or facilitate adaptive divergence is a central goal in evolutionary biology, especially in non-model organisms. We tested whether changes in dynamics of gene flow (historical vs contemporary) caused population isolation and examined local adaptation in response to environmental selective forces in fragmented Rhododendron oldhamii populations. Variation in 26 expressed sequence tag-simple sequence repeat loci from 18 populations in Taiwan was investigated by examining patterns of genetic diversity, inbreeding, geographic structure, recent bottlenecks, and historical and contemporary gene flow. Selection associated with environmental variables was also examined. Bayesian clustering analysis revealed four regional population groups of north, central, south and southeast with significant genetic differentiation. Historical bottlenecks beginning 9168-13,092 years ago and ending 1584-3504 years ago were revealed by estimates using approximate Bayesian computation for all four regional samples analyzed. Recent migration within and across geographic regions was limited. However, major dispersal sources were found within geographic regions. Altitudinal clines of allelic frequencies of environmentally associated positively selected outliers were found, indicating adaptive divergence. Our results point to a transition from historical population connectivity toward contemporary population isolation and divergence on a regional scale. Spatial and temporal dispersal differences may have resulted in regional population divergence and local adaptation associated with environmental variables, which may have played roles as selective forces at a regional scale.
Subject(s)
Adaptation, Biological/genetics , Gene Flow , Plant Dispersal/genetics , Reproductive Isolation , Rhododendron/classification , Rhododendron/genetics , Bayes Theorem , Biological Evolution , Environment , Expressed Sequence Tags , Genetic Drift , Genetic Variation , Microsatellite Repeats , Multigene Family , Phylogeography , Sequence Analysis, DNA , TaiwanABSTRACT
Kondo impurities provide a nontrivial probe to unravel the character of the excitations of a quantum spin liquid. In the S = 1/2 Kitaev model on the honeycomb lattice, Kondo impurities embedded in the spin-liquid host can be screened by itinerant Majorana fermions via gauge-flux binding. Here, we report experimental signatures of metallic-like Kondo screening at intermediate temperatures in the Kitaev honeycomb material α-RuCl3 with dilute Cr3+ (S = 3/2) impurities. The static magnetic susceptibility, the muon Knight shift, and the muon spin-relaxation rate all feature logarithmic divergences, a hallmark of a metallic Kondo effect. Concurrently, the linear coefficient of the magnetic specific heat is large in the same temperature regime, indicating the presence of a host Majorana metal. This observation opens new avenues for exploring uncharted Kondo physics in insulating quantum magnets.
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BACKGROUND: Mutations in 6 genes have been identified as being part of the etiology of amelogenesis imperfecta (AI) with various phenotypes in an isolated condition. Among them the FAM83H gene is the major contributor to the etiology of AI with unknown function. OBJECTIVE: This study aims to determine the phenotypic and molecular characterization of Chinese AI patients and to analyze the structure and function of the FAM83H protein. METHODS: We enrolled 6 hypocalcified AI and 3 hypoplastic AI families from the Chinese population. Mutation analysis was performed by amplifying and sequencing all exons including intron-exon borders for FAM83H and ENAM genes. Structural modeling and function analysis on the FAM83H protein were carried out by bioinformatic processing. RESULTS: No obvious anterior open bite was observed in all the investigated individuals. Five mutations (c.906T>G, c.924dupT, c.973C>T, c.1354C>T and c.2029C>T) in the C-terminal of the FAM83H gene were revealed, respectively, in 5 out of 6 hypocalcified AI families, and a splicing mutation c.534 + 1G>A in the ENAM gene was identified in 1 out of 3 hypoplastic AI families. Structural models of the N- and C-terminal regions of FAM83H were generated by homology modeling. The predicted structure of the FAM83H N-terminal shows resemblance to that of glycosyltransferases with GT-A folds, and the predicted structure of the FAM83H C-terminal possesses similarity to type I collagen protein. CONCLUSIONS: To our knowledge, this is the first report of AI with specific molecular variations in families of Chinese descent. Our study provides new insights into the structure and function of the FAM83H protein.
Subject(s)
Amelogenesis Imperfecta/genetics , Asian People , Mutation , Proteins/genetics , Amelogenesis Imperfecta/ethnology , Amelogenesis Imperfecta/pathology , Amino Acid Sequence , China/epidemiology , DNA Mutational Analysis , Databases, Protein , Extracellular Matrix Proteins , Family Health , Female , Humans , Male , Models, Molecular , Molecular Sequence Data , Pedigree , Protein Structure, Tertiary , Proteins/chemistry , Sequence AlignmentABSTRACT
We report muon spin rotation (µSR) and infrared spectroscopy experiments on underdoped BaFe1.89Co0.11As2 which show that bulk magnetism and superconductivity (SC) coexist and compete on the nanometer length scale. Our combined data reveal a bulk magnetic order, likely due to an incommensurate spin density wave (SDW), which develops below T(mag)≈32 K and becomes reduced in magnitude (but not in volume) below Tc=21.7 K. A slowly fluctuating precursor of the SDW seems to develop already below the structural transition at T(s)≈50 K. The bulk nature of SC is established by the µSR data which show a bulk SC vortex lattice and the IR data which reveal that the majority of low-energy states is gapped and participates in the condensate at TâªT(c).
ABSTRACT
BACKGROUND: Dentin phosphoprotein (DPP) is the most abundant non-collagenous protein in dentin, which is highly phosphorylated and plays key roles in dentin biomineralization. The aetiology of isolated hereditary dentin disorders in most affected families is largely unknown and the association between DPP and dentin disorders has not been well established. This study aims to determine whether there are some involvements for DPP mutations in inherited dentin disorders and to clarify the sequence variation patterns of DPP in normal population. METHODS: Genomic DNA was analysed in eight families with hereditary dentin disorders and 110 individuals in the normal population. The full coding sequence of DPP was amplified by polymerase chain reaction (PCR) and screened for mutations and variations by direct sequencing and TOPO TA-cloning sequencing. RESULTS: Five frameshift mutations in DPP coding region were identified in five of the eight families. The mutations co-segregated with the disease phenotypes in affected families and were not found in 220 control chromosomes. In the normal population, we revealed 14 in-frame indels (insertion/deletion), six non-synonymous single nucleotide polymorphisms (SNPs), and five synonymous SNPs in the DPP coding region. These variants display extensive linkage disequilibrium and constitute a total of 15 haplotypes with three predominant haplotypes in the investigated normal population. CONCLUSIONS: Our data provide the first evidence that DPP mutations can cause hereditary dentin disorders and suggest that in-frame length variations and missense SNPs in DPP have no obvious pathogenetic effects on dentin formation.
Subject(s)
Dentin Dysplasia/genetics , Extracellular Matrix Proteins/genetics , Frameshift Mutation , Adult , Child , Child, Preschool , DNA/chemistry , DNA/genetics , Female , Genetic Variation , Haplotypes , Humans , Male , Pedigree , Phosphoproteins , Polymerase Chain Reaction , Polymorphism, Genetic , Sequence Analysis, DNA , SialoglycoproteinsABSTRACT
Objective: To illuminate the effect of NALP3 inflammasome on regulating the expression of cytokines of macrophages in periodontitis. Methods: RAW264.7 cells were cultured and divided into three groups. The first group stayed normal as control, the second group was stimulated by 1 mg/L Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS), the third group was pretreated with AC-YVAD-CMK (caspase-1 inhibitor) before stimulated with 1 mg/L Pg LPS. RAW264.7 cells pretreated with various concentrations (0, 5, 10, 25, 50, 75, 100, 200 µmol/L) of AC-YVAD-CMK for 2 h, and stimulated by 1 mg/L Pg LPS for 24 h in the third group. After that, cell survival rate were detected by cell counting kit-8. Every group cells gene transcription of NALP3 and interleukin-1ß (IL-1ß) were detected by quantitative real-time PCR (qPCR) after 6 h, protein expression of NALP3 and IL-1ß were separately detected by Western blotting and enzyme linked immunosorbent assay (ELISA) after 24 h, respectively. Results: It is observed that treatment with 5, 10, 25, 50, 75, 100, 200 µmol/L AC-YVAD-CMK did not significantly affect the viability of RAW264.7 cells. qPCR showed that mRNA expression of IL-1ß level (1.03±0.08, 5.48±0.22, 4.31±0.20) and NALP3 level (0.96±0.05, 2.62±0.44, 1.73±0.09). Western blotting showed that protein expression of NALP3 level (1.00±0.10, 2.34±0.04, 1.64±0.04), ELISA showed protein secretion of IL-1ß level ([40.20±0.25], [61.50±1.81], [52.40±1.91] ng/L). After stimulated by Pg LPS, mRNA and protein expression of IL-1ß (P<0.01, P<0.01) and NALP3 (P<0.01, P<0.01) significantly increased; but the expression of IL-1ß (P=0.002, P=0.027) and NALP3 (P<0.01, P<0.01) were decreased when pretreated with AC-YVAD-CMK. Conclusions: NALP3 inflammasome signal pathway can be activated by Pg LPS in RAW264.7. Block of the pathway can inhibit Pg LPS-induced secretion of cytokines.
Subject(s)
Amino Acid Chloromethyl Ketones/pharmacology , Cytokines/metabolism , Inflammasomes/pharmacology , Lipopolysaccharides/pharmacology , Macrophages/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Periodontitis/metabolism , Porphyromonas gingivalis/chemistry , Amino Acid Chloromethyl Ketones/administration & dosage , Cell Survival , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Macrophages/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Periodontitis/pathology , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Serpins/pharmacology , Signal Transduction , Time Factors , Viral Proteins/pharmacologyABSTRACT
Cherubism is a benign lesion that causes painless symmetrical enlargement of the jaws, usually with a familial tendency. We describe in two Chinese families two cases of the aggressive form of cherubism with extensive swelling on both sides of the mandible, typical microscopic findings, and apparent familial history.
Subject(s)
Cherubism/pathology , Mandible/pathology , Mandibular Diseases/pathology , Adult , Cherubism/diagnostic imaging , Cherubism/surgery , Child , Female , Humans , Male , Mandible/diagnostic imaging , Mandible/surgery , Mandibular Diseases/diagnostic imaging , Mandibular Diseases/surgery , Radiography , Treatment OutcomeSubject(s)
Deafness , Hearing Loss , Disability Evaluation , Hearing Loss/diagnosis , Humans , Patient Reported Outcome MeasuresABSTRACT
We report field-dependent magnetization measurements on monolayers of [Dy(Pc)2] on quartz, prepared by the Langmuir-Blodgett technique. The films are thoroughly characterized by means of X-ray reflectivity and atomic force microscopy. The magnetisation of the sample is measured through the magnetic circular dichroism of a ligand-based electronic transition.