The protective role of curcumin in human dental pulp stem cells stimulated by lipopolysaccharide via inhibiting NF-κB p65 phosphorylation to suppress NLRP3 inflammasome activation.

OBJECTIVES: This study aims to investigate the anti-inflammatory effect of curcumin and underlying mechanisms regarding the modulation of the nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: The impact of curcumin on the viability of hDPSCs was evaluated. The effect of curcumin on the expression of IL-1ß and NLRP3 in hDPSCs stimulated by lipopolysaccharide (LPS) was assessed. Then, LPS-primed hDPSCs were pre-treated with curcumin before ATP triggering NLRP3 inflammasome activation, and NLRP3 inflammasome-related mediators were assessed. The mechanism of curcumin inactivation of LPS plus ATP-induced inflammasome associated with NF-κB pathway was explored. The NF-κB pathway related pro-inflammatory mediators at mRNA and protein levels were evaluated. The expression of NF-κB p65 and phosphorylation p65 was visualized after curcumin or NF-κB inhibitor administrating respectively in hDPSCs with an activated NLRP3 inflammasome. Statistical analysis was performed. RESULTS: While curcumin at the concentration of 0.5-5 µM showed no obvious impact on the viability of hDPSCs, it significantly decreased IL-1ß and NLRP3 mRNA expression in LPS-induced hDPSCs in a dose-dependent manner. Curcumin significantly inhibited the LPS plus ATP-primed NLRP3 inflammasome activation in hDPSCs (NLRP3, ASC, caspase-1, and IL-1ß). Curcumin evidently attenuated the LPS plus ATP-induced expression of NF-κB pathway-related pro-inflammatory mediators (IL-6, IL-8, TNF-α, and COX-2). Furthermore, curcumin effectively reduced p65 phosphorylation, which acts as an NF-κB inhibitor in hDPSCs with an activated NLRP3 inflammasome. CONCLUSIONS: Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs. CLINICAL RELEVANCE: Curcumin may have therapeutic potential in pulp inflammation.

Characteristics of Allergen Components of Dermatophagoides pteronyssinus in Shrimp and Mite Co-Sensitized Patients in Southern China.

INTRODUCTION: Dermatophagoides pteronyssinus (Dp) and shrimp are common air allergens and allergenic food sources, respectively, in southern China. This study aimed to analyze the specific immunoglobulin E (sIgE) characteristics and relationships of Dp components among co-sensitized patients with Dp and shrimp. MATERIALS AND METHODS: Serum samples were collected from 112 patients with Dp sensitization (61 with shrimp sensitization and 51 without) from southern China. The sIgE concentrations of Dp and shrimp crude extracts were determined by ImmunoCAP, and the sIgE of Dp allergen components (Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der p 21, and Der p 23) was detected by protein chip. RESULTS: Overall, in the Dp-allergic patients, Der p 1 had the highest positive rate (72.3%), followed by Der p 2 (65.2%), Der p 23 (46.4%), Der p 7 (32.14%), Der p 21 (29.46%), Der p 5 (22.32%), and Der p 10 (17.86%). Compared with that in the shrimp nonsensitized group, the positive rate of sIgE for Der p 10 (27.87% vs. 5.88%, p = 0.002) in the shrimp sensitization group was significantly higher; however, the positive rate of sIgE for Der p 7 (22.95% vs. 43.14%, p = 0.023) was significantly lower. Moreover, the concentration of sIgE for Der p 10 increased statistically in the shrimp-sensitized group. The correlation analysis also showed that shrimp sensitization was significantly correlated with Der p 10. CONCLUSION: Among patients with Dp sensitization, Der p 1 had the highest positive rate, followed by Der p 2 and Der p 23. Meanwhile, Der p 10 may play an important role in patients with shrimp sensitization, while Der p 7 may be the meaningful allergen component in patients with Dp sensitization alone. In general, component-resolved diagnosis technology in clinical practice can effectively guide patients with polysensitization to avoid allergic substances.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

BACKGROUND: Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. METHODS: We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. RESULTS: LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. CONCLUSION: We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

Associations of Four sensitization patterns revealed by Latent Class Analysis with Clinical symptoms: A multi-center study of China.

Background: Because of the significant regional differences in the distribution of allergens, the relationship between anaphylaxis and allergic sensitization is complex in China. Using this large-scale epidemiologic survey, we explore the potential patterns of sensitization to common allergens in mainland China and investigate their relationship with various clinical symptoms. Method: The participants were recruited from 13 medical centers in mainland China from October 2019 to June 2021. Skin prick test (SPT) results that cover 18 common allergens were utilized to diagnose atopic sensitization. The demographic characteristics and clinical information were collected through questionnaires during routine medical follow-up. Latent class analysis (LCA) was conducted to determine the optimal sensitization patterns. The logistic regression was used to assess the associations of different sensitization patterns with allergy symptoms. Findings: A total of 1089 patients who had a positive SPT to at least one of 18 allergens were included for formal analysis. An optimal LCA model with 4 classes was obtained in this study, and the corresponding labels were as follows: Class1, house dust mite sensitization; Class2, low pollen sensitization; Class3, middle pollen sensitization; Class4, high pollen sensitization. The prevalence of different classes varied widely in geographical distribution, which was characterized by Class1 being very common in south and east as well as Class2 in north and west of China. Compared with patients in Class1, those in middle and high pollen sensitization clusters had the higher odds ratios (ORs) of allergic rhinitis and allergic conjunctivitis when controlling for other confounders. However, there was no significant difference between low pollen sensitization and house dust mite sensitization groups in the risks for various clinical performances except dermatitis. Additionally, the adjusted ORs (95% confidence interval) of allergic conjunctivitis and dermatitis for participants in pollen sensitization clusters (Class2, 3 and 4) were 1.56 (1.18, 2.06) and 1.43 (1.09, 1.88) respectively compared with those in Class1. Interpretation: In this study, we identified four sensitization clusters with specific risks of various clinical symptoms using common allergens by adopting LCA. Our findings may contribute to improved diagnosis and potential immunotherapy approaches to allergy in mainland China. Funding: This study was supported by the National Natural Science Foundation of China (81802076 and 81871736), the Guangzhou Science and Technology Foundation (202102010327), the Foundation of SKLRD (MS-2019-06 and Z-2022-09), and the Foundation of GYYY (ZH201904) and ZNSA-2020012.

Three patterns of sensitization to mugwort, timothy, birch and their major allergen components revealed by Latent class analysis.

BACKGROUND: Mugwort, timothy, and birch are commonly spread pollen allergens across China. Although several studies have described the rates of sensitization to mugwort, timothy, and birch in China, most of them just on specific whole-allergen extracts but little was known about the co-sensitization characteristics of its allergen components. This study aimed to explore the patterns of sensitization to mugwort, timothy, birch, and their major allergen components. METHOD: Serum specific IgE (sIgE) levels of allergen components of mugwort, timothy, birch, and cross-reactive carbohydrate determinants (CCD) were detected in 160 patients whose serum showed positive results to at least one of mugwort, timothy, and birch allergens via EUROBlotMaster system. Skin prick testing was utilized to assess the allergic reaction of grass, weed, and tree allergens. Latent class analysis was used to identify underlying patterns of sensitization to a series of allergen components and their corresponding extracts. RESULTS: 88.8% of patients with allergic rhinitis and/or asthma were positive for mugwort-sIgE, 30% for timothy-sIgE, and 32.5% for birch-sIgE. By using the LCA model, three sensitization patterns as "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized", "Timothy, mugwort, and CCD co-sensitized", "Mugwort and Art v 1 co-sensitized" were revealed based on optimal statistical fit in this study. Compared with other clusters, participants in "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized" pattern were associated with higher sensitization rates of common grass and tree pollens allergen. The spearman's coefficient between CCD and timothy was larger than the corresponding values of CCD with mugwort or birch. CONCLUSION: CCD and profilin, as minor allergens in pollens, were associated with other pollen sIgE false positives presumably due to cross-reactivity. Patients sensitized with profilin had a significantly higher risk of sensitization to other pollens.

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Understanding changes in soil enzyme activities and ecoenzymatic stoichiometry is important for assessing soil nutrient availability and microbial nutrient limitation in mountain ecosystems. However, the variations of soil microbial nutrient limitation across elevational gradients and its driving factors in subtropical mountain forests are still unclear. In this study, we measured soil properties, microbial biomass, and enzyme activities related to carbon (C), nitrogen (N), and phosphorus (P) cycling in Pinus taiwanensis forests at different altitudes of Wuyi Mountains. By analyzing the enzyme stoichiometric ratio, vector length (VL), and vector angle (VA), the relative energy and nutrient limitation of soil microorganisms and its key regulatory factors were explored. The results showed that ß-glucosaminidase (BG) activities increased along the elevational gradient, while the activities of ß-N-acetyl glucosaminidase (NAG), leucine aminopeptidase (LAP), acid phosphatase (AcP) and (NAG+LAP)/microbial biomass carbon (MBC) and AcP/MBC showed the opposite trend. Enzyme C/N, enzyme C/P, enzyme N/P, and VL were enhanced with increasing elevation, while VA decreased, indicating a higher degree of microbial P limitation at low elevation and higher C limitation at high elevation. In addition, our results suggested that dissolved organic carbon and microbial biomass phosphorus are critical factors affecting the relative energy and nutrient limitation of soil microorganisms at different elevations. The results would provide a theoretical basis for the responses of soil carbon, nitrogen, and phosphorus availability as well as the relative limitation of microbial energy and nutrition to elevational gradients, and improve our understanding of soil biogeochemical cycle process in subtropical montane forest ecosystems.

The efficacy of platelet-rich fibrin as a scaffold in regenerative endodontic treatment: a retrospective controlled cohort study.

BACKGROUND: Blood Clot (BC) or platelet concentrates have been used as scaffold in regenerative endodontic treatment (RET). The aim of this retrospective study was to compare the performance of platelet-rich fibrin (PRF) with BC in inducing root development and periapical lesion healing after tooth revascularization. METHODS: Five patients receiving RET using PRF as a scaffold were matched 1:1 to a previous cohort of 5 patients who underwent tooth revascularization by provoking periapical bleeding. Clinical signs and symptoms were examined at follow-ups. Periapical lesion healing and root development were monitored radiographically. The resolution of clinical signs and symptoms as well as periapical radiolucency was observed in all patients (100%). RESULTS: Root elongation, dentinal wall thickening and apex closure were found in most cases (80% in both groups). There was no significant difference between the groups in terms of clinical sign resolution, root development and periapical healing. CONCLUSIONS: Within the limits of this study, PRF achieved comparable outcomes to BC in terms of clinical sign and symptom resolution, periapical lesion healing and continued root development in RET.

Urbanization gradient of selected pharmaceuticals in surface water at a watershed scale.

Ubiquitous detection of pharmaceuticals in the aquatic environment around the world raises a great public concern. Aquatic residuals of pharmaceuticals have been assumed to relate to land use patterns and various human activities within a catchment or watershed. This study generated a gradient of human activity in the Jiulong River watershed, southeastern China by urban land use percentage in 20 research subwatersheds. Thirty-three compounds from three-category pharmaceuticals [26 compounds of 5 antibiotic groups, 6 compounds of non-steroidal anti-inflammatory drugs (NSAIDs), and 1 compound of respiratory system drugs (RSDs)] were quantified in stream water before the research subwatershed confluences with two sampling events in dry and wet seasons. In total, 27 out of the 33 pharmaceutical compounds of interest were found in stream waters. Seasonality of instream pharmaceuticals was observed, with less compounds and lower concentrations in the wet season sampling event than in the dry season one. Urban land use in the research subwatershed was identified as the main factor influencing in stream pharmaceutical concentrations and composition regardless of season. Rural land uses contributed a mixture of human and veterinary pharmaceuticals possibly from agricultural application of manure and sewage sludge and aquaculture in the research subwatersheds. Erythromycin in both sampling events showed medium to high risks to aquatic organisms. Results of this study suggest that urban pharmaceutical management, such as a strict prescription regulations and high-efficient removal of pharmaceuticals in wastewater treatment, is critical in reducing aquatic pharmaceutical loads.

Radiographic, Histologic, and Biomechanical Evaluation of Combined Application of Platelet-rich Fibrin with Blood Clot in Regenerative Endodontics.

INTRODUCTION: No in vivo study has been reported on the mechanical reinforcement of a tooth after regenerative endodontic treatment (RET). The present work aimed to evaluate the concurrent use of platelet-rich fibrin (PRF) with a blood clot (BC) in RET concerning periapical healing, root development, and tooth structural reinforcement. METHODS: In our study, 24 premolars from 3 beagle dogs were assigned into control, BC, and PRF + BC groups. Periapical healing was monitored with quantitative measurements of root elongation and thickening radiographically. Tooth biomechanical integrity was assessed with the fracture resistance test. Histologic evaluation was conducted. RESULTS: There was a significant difference among the periapical radiolucency decreasing rate of the control (43.75%) and the BC (100%) and PRF + BC (100%) groups (P < .05). The increase of root length and thickness in both the BC and PRF + BC groups was significantly greater than that in the control group (P < .05). No significant difference was detected between the 2 experimental groups regarding periapical healing or root development (P > .05). Teeth in the BC (249.3 ± 64.1 N) and PRF + BC (281.7 ± 37.8 N) groups had significantly higher fracture resistance than those in the control group (108.5 ± 23.3 N) (P < .05). No significant difference was revealed between the BC and PRF + BC groups (P > .05). Histologic evidence of cementumlike tissue deposition along the canal wall with scattered bonelike tissue in the canal was observed. CONCLUSIONS: Either a combination of PRF with BC or BC alone could improve periapical healing, induce root development, and reinforce tooth structure. No additional benefit of PRF to BC in RET was found.

Histologic and Immunohistochemical Findings of a Human Immature Permanent Tooth with Apical Periodontitis after Regenerative Endodontic Treatment.

Specimens of human immature permanent teeth after regenerative endodontic treatment (RET) are sparse. This case report describes the histologic and immunohistochemical findings of tissue formed in the canal space of a human immature permanent tooth with apical periodontitis after RET. A patient presenting with immature human permanent tooth #29 with apical periodontitis underwent RET. At the 10-month follow-up visit, radiographic examination revealed complete resolution of the periapical lesion, marked narrowing of the apical foramen, increased thickness of the canal walls, and minimal lengthening of the root. Notably, the tooth regained pulp sensibility. Tooth #29 was extracted for orthodontic reasons and processed for histologic and immunohistochemical examination. The canal space was filled with newly formed cementumlike tissue, bonelike tissue, and fibrous connective tissue. The apical closure, thickness, and length increment of the root were caused by the deposition of cementumlike tissue without dentin. Furthermore, neurons and nerve fibers were observed in the canal space; this observation was confirmed by immunohistochemistry. Based on the findings in the present case, after RET, the newly formed tissues in the canal space of the human immature permanent tooth with apical periodontitis were primarily fibrous connective tissue, cementumlike tissue, and bonelike tissue. Nerve regeneration was identified.