The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

The repair of the periodontal membrane is essential for the successful management of periodontal disease and dental trauma. Emdogain^® (EMD) is widely used in periodontal therapy due to its ability to promote repair. Despite substantial research, the cellular and molecular mechanisms underlying EMD's effects, particularly at the single-cell resolution, remain incompletely understood. This study established a delayed tooth replantation model in rats to investigate these aspects. Tooth loss rate and degree of loosening were evaluated at 4 and 8 weeks. Micro-CT, HE staining, TRAP staining, and immunofluorescence staining were evaluated to assess EMD's efficacy. Single-cell sequencing analyses generated single-cell maps that explored enrichment pathways, cell communication, and potential repair mechanisms. Findings indicated that EMD could reduce the rate of tooth loss, promote periodontal membrane repair, and reduce root and bone resorption. Single-cell analysis revealed that EMD promotes the importance of Vtn+ fibroblasts, enhancing matrix and tissue regeneration functions. Additionally, EMD stimulated osteogenic pathways, reduced osteoclastic activity, and promoted angiogenesis-related pathways, particularly bone-related H-type vessel expression in endothelial cells. Gene modules associated with angiogenesis, osteogenesis, and odontoblast differentiation were identified, suggesting EMD might facilitate osteogenesis and odontoblast differentiation by upregulating endothelium-related genes. Immune cell analysis indicated that EMD did not elicit a significant immune response. Cell communication analysis suggested that EMD fostered pro-regenerative networks driven by interactions between mesenchymal stem cells, fibroblasts, and endothelial cells. In conclusion, EMD proves to be an effective root surface therapy agent that supports the restoration of delayed replantation teeth.
Animals ; Tooth Replantation/methods* ; Rats ; Dental Enamel Proteins/pharmacology* ; Single-Cell Analysis ; Rats, Sprague-Dawley ; X-Ray Microtomography ; Osteogenesis/drug effects* ; Male ; Periodontal Ligament/drug effects*

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective:To analyze the viral nucleic acid and cytokines in 12 children with 2019-nCoV infection.Methods:Clinical and laboratory data of the children diagnosed with 2019-nCoV infection in Guangzhou Women and Children′s Medical Center from January to April 2020 were retrospectively analyzed. Throat and anal swabs were collected on alternate days for the detection of 2019-nCoV nucleic acid by fluorescence quantitative PCR. Flow cytometry was used to detect serum cytokines including IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, TNF-α and TNF-β during the early (both throat and anal swab tests were positive), the intermediate (throat swab test was negative, while anal swab test remained positive), and the convalescence (both throat and anal swab tests were negative) stages of infection.Results:A total of 12 children were enrolled in this study. The male-to-female ratio was 5∶1. The average age was (7.0±4.3) years. There were two asymptomatic, five mild and five common cases. No severe or critical cases were involved. Initially, throat and anal swab nucleic acid tests were simultaneously positive in nine children newly diagnosed in our hospital and the median time of viral shedding in throat swab was longer than that in throat swab [32 (4.5, 45.0) d vs 3 (2, 9) d, Z=11.0, P=0.010]. The median difference of viral shedding time between anal swab and pharyngeal swab was 25.5 (1.5, 42.8) d. The overall levels of serum cytokines IL-17A, IL -4 and IL-5 in different stages of the disease (early, intermediate and convalescence stage) were statistically different ( Z or F, P values were 8.33, 0.016; 5.36, 0.010 and 6.56, 0.004, respectively), and a significant increase was observed in the intermediate stage of infection. IL-17F, IL-2 and IL-22 were all increased during the infection, but there was no significant statistical difference among the three stages ( P>0.05). Conclusions:It was noted that intestinal viral shedding needed a longer time. Although the infectivity has not been determined, higher requirements have been put forward for disease prevention and control. Cytokines secreted by Th2 and Th17 cells were involved in the immune response in children with non-severe 2019-nCoV infection. Monitoring viral shedding and cytokine changes in pediatric patients would be conducive to disease assessment.

Objective To discuss the image of indocyanine green angiography (ICGA) about high myopia. Methods Tweenty seven patients (54 eyes) with high myopia underwent ocular examination, fundus color photography, simultaneous ICGA and fluorescein angiography (FFA) with the confocal scanning laser ophthalmoscope.The findings for the two modes of amgiographies were compared. Results Lacquer crack was evident on ICGA in 19 eyes among which the focal, plaque choroidal neovascularization (CNV) were apparent in the middle part of lacquer cracks in 10 eyes (52.6%) .In comparison the lacquer cracks were seen in only 7 eyes on FFA. Choroidal capillary atrophy was seen on ICGA and FFA in 14 eyes and ICGA shew thick choroidal vessels in 3 eyes. Conclusion ICGA is superior to FFA for showing choroidoretinal degeneration and atrophy,lacquer crack and CNV in high myopic eyes, and conduce to evaluating prognosis.

Purpose To discuss changes of macular choriocapillaris hemodynamics in AMD. Methods Eighty six eyes of 86 patients underwent ICGA,including macular drusen in 15 eyes of 15 patients,exudative AMD in 52 eyes of 52 patients,atrophic AMD in 19 eyes of 19 patients,for the observation of macular choriocapillaris perfusion. Results Choriocapillaris filling phase (CFP) of exudative AMD was obviously longer than that of eyes with normal, atrophic AMD and drusen groups ( P

ObjectiveTo observe and estimate the image characters of indocyanine green angiography (ICGA) and fundus fluorescein angiography (FFA) in atrophic age-related macular degeneration(AMD) and macular drusen.MethodsFFA, ICGA and fundus photography were performed on 95 eyes of 73 atrophic AMD patients, including 19 patients (26 eyes) with depigmentation and atrophy of retinal pigment epithelium (RPE), 15 (30 eyes) with macular drusen, and 39 (39 fellow eye) with unilateral exudative AMD. ResultsIn 26 eyes with depigmentation and atrophy of RPE, the result of FFA of 24 eyes with depigmentaion showed patch hyperfluorescence, and of ICGA showed patch hyperfluorescence and hypofluorescence on the late photographs; in 2 eyes with maplike atrophy of RPE, the result of FFA showed patch hyperfluorescence, and of ICGA showed choriocapillaris defect with sharply demarcated boundaries and hypofluorescence of large choroidal vessels. In 30 eyes with macular drusen, the result of FFA of 8 eyes with hard drusen showed hyperfluorescence, and of ICGA showed patch and spot hyperfluorescence; the result of FFA of 16 eyes with soft drusen showed hyperfluorescence, and of ICGA showed persistent patch hypofluorescence intermixed with cluster hyperfluorescence; and the result of FFA of 6 eyes with both soft and hard drusen showed hyperfluorescence, and of ICGA showed patch hyperfluorescence intermixed with hypofluorescence. When it was hypofluorescence in ICGA in patients with macular drusen, larger quantity and range of fluorescence were found in FFA than in ICGA; when it was hyperfluorescence in ICGA, smaller quantity and range of fluorescence were found in FFA than in ICGA. In 39 fellow eyes of unilateral exudative AMD, 32 or 31 eyes, examined by ICGA or FFA, had abnormal fluorescence of drusen and depigmentation and atrophy of RPE damage.ConclusionsSimultaneous examination of ICGA and FFA can be useful for accurate evaluation of fundus image characters of types of angiography in atrophic AMD.