1.Discovery of a novel AhR-CYP1A1 axis activator for mitigating inflammatory diseases using an in situ functional imaging assay.
Feng ZHANG ; Bei ZHAO ; Yufan FAN ; Lanhui QIN ; Jinhui SHI ; Lin CHEN ; Leizhi XU ; Xudong JIN ; Mengru SUN ; Hongping DENG ; Hairong ZENG ; Zhangping XIAO ; Xin YANG ; Guangbo GE
Acta Pharmaceutica Sinica B 2025;15(1):508-525
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.
2.Single-cell sequencing systematically analyzed the mechanism of Emdogain on the restoration of delayed replantation periodontal membrane.
Yanyi LIU ; Yuhao PENG ; Lanhui CHEN ; Yangfan XIANG ; Ximu ZHANG ; Jinlin SONG
International Journal of Oral Science 2025;17(1):33-33
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
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Tooth Replantation/methods*
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Rats
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Dental Enamel Proteins/pharmacology*
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Single-Cell Analysis
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Rats, Sprague-Dawley
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X-Ray Microtomography
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Osteogenesis/drug effects*
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Male
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Periodontal Ligament/drug effects*
3.Discussion on TCM Etiology and Pathogenesis of Cognitive Dysfunction from the of Perspective Microbiota-gut-brain Axis Based on"Spleen Can't Regulate Spirit"
Lanhui ZHENG ; Qi ZHANG ; Boyu ZHANG ; Dandan FENG ; Jiayao LUO ; Tong YANG ; Hua SUI ; Yan WANG ; Qingquan SUN ; Sheng LI ; Shuyuan LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(6):18-23
Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.
4.Research progress of TCM in treating radiation enteritis based on intestinal microecology
Zhezhe ZHANG ; Litian MA ; Canjun ZHAO ; Lanhui ZHANG ; Jin ZHENG
International Journal of Traditional Chinese Medicine 2022;44(8):959-961
Patients with radioactive enteritis generally have certain intestinal microecological imbalance. Traditional Chinese Medicine (TCM) has showed good advantage in regulating intestinal microbial flora. In clinical practice, patients are treated based on syndrome differentiation of heat toxin damaging collaterals, cold-heat mixed syndrome, spleen deficiency and dampness stagnation, spleen and kidney yang deficiency, yin deficiency and body fluid deficiency. The Baitouweng Decoction, Wumei Pill, Sijunzi Decoction are the common prescriptions. TCM can promote the balance of intestinal microecology and treat digestive diseases such as radioactive enteritis, by improving the abundance of intestinal flora, inhibiting the level of inflammatory cytokines, and playing the role of probiotics and immune regulation.
5.Identification of the core promoter of the pmel gene of Bashang long-tail chickens.
Xiaohui LIU ; Rongyan ZHOU ; Yongdong PENG ; Chuansheng ZHANG ; Lanhui LI ; Xianglong LI
Chinese Journal of Biotechnology 2018;34(11):1750-1759
To explore the activity of the pmel core promoter of Bashang long-tail chickens, we constructed dual-luciferase expression vectors and transiently transfected into DF1 cells with Lipofectamine 2000. We measured the luciferase activity with the dual-luciferase detection kit. The 1 268 bp fragment in 5-flanking region of the pmel gene in Bashang long-tail chickens was cloned. The region from -1 200 bp to +68 bp included 2 CpG islands and multiple transcription factor binding sites. We constructed 9 expression vectors with different promoter regions and a mutant vector of the core promoter region of the pmel gene of Bashang long-tail chickens. The core promoter region from -840 bp to +68 bp was identified in the pmel gene. The region from -590 to -525 bp negatively regulated the pmel gene during the transcription process. The -840--590 bp and -525--266 bp regions were positive regulatory regions. The polymorphic sites (-456, -435, -410, -374 and -341) had a significant effect on the promoter activity of the pmel gene.
Animals
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Chickens
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genetics
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Cloning, Molecular
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CpG Islands
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Luciferases
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Promoter Regions, Genetic
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gp100 Melanoma Antigen
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genetics
6.Correlation between Helicobacter pylori DNA positive detection in bile of gallbladder and intragastric Helicobacter pylori's colony
Huaibin GUO ; Wanxing ZHANG ; Lanhui WANG ; Wenke TAN
Clinical Medicine of China 2010;26(5):501-503
Objective To study the relationship between Helicobacter pylori (Hp) DNA positive detection in bile of gallbladder and intragastric Hp's colony and its plausible mechanism.Methods Sixty patients of gallbladder innocence diseases were recruited in the case group and 30 health populations were recruited in the control group.13CPDB was used to detect the infection of Hp.The cytotoxin associated gene antigen (cagA) in gall and gall-stone were detected through PCR.The empty function was tested through B ultrasound.Results The infection rate of Hp in all cases is 50.0% (30/60) and 7 of 30 bile (23.3%) ,1 of 30 gallstones (3.3%) were positive for Hp cag-A by PCR analysis in positive Hp infection group,with none of the 30 bile were positive in negative group( x2 = 5.822 ,P < 0.05 ).The contraction rate of gallbladder of Hp positive group ( 56.8 ± 17.1 ) %was lower than negetive group' s ( 69.4 ± 13.1 ) % and the control group' s (63.3 ± 17.1 ) % ( F = 5.633,P <0.05).Conclusions Hp DNA is present in bile of gallbladder,and is related with Hp infection in stomach.Impairment of the gallbladder empty function may be related with Hp infection.
7.Effect of different carbon dioxide pneumoperitoneum pressure on postoperative shoulder pain occurrence following laparoscopic cholecystectomy
Jinghua ZHANG ; Yuemin CAO ; Wenke TAN ; Jianjun JIANG ; Lanhui WANG ; Wanxing ZHANG ; Huiyan MENG
Chinese Journal of General Surgery 1997;0(04):-
Objective To determine if the carbon dioxide (CO 2) pressure used in laparoscopic cholecystectomy (LC) has any effect on the occurrence of postoperative shoulder pain. Methods One hundred and twenty consecutive patients undergoing LC were prospectively divided into three groups(40 patients in each group): Patients in group A underwent LC with 10 mm Hg of CO 2, those in group B with 12 mm Hg of CO 2, and in group C with 14 mm Hg of CO 2. PaO 2?PaCO 2?pH before and after LC were recorded. Shoulder pain was recorded on a visual analogue pain scale 1,3,6,12,24,48,72,96 h after operation. Results The intraoperative CO 2 consumption was significantly higher in group C (F=11.38,P
8.Determination of gentiopicrin, palmatine hydrochloride and berberine hydrochloride in Ertong Ⅱ Oral Liquid by RP-HPLC with gradient elution
Lanhui SHEN ; Tao SHI ; Aifeng ZOU ; Jinshan REN ; Shengqiang ZHANG ;
Chinese Traditional Patent Medicine 1992;0(04):-
AIM: To establish the method for determination of gentiopicrin, palmatine hydrochloride and berberine hydrochloride in Ertong Ⅱ Oral Liquid (Cortex Phellodendri, Radix Gentianae, Rhizoma Anemarrhenae, etc.) by RP HPLC. METHODS: The column was a Diamonsil TM C 18 column (250mm?4.6mm, 5?m); the mobile phase was CH 3CN H 3PO 4 C 6H 15 N H 2O; The ultraviolet detection was set at 270nm; the flow rate was 1mL?min -1 . RESULTS: The linear ranges of gentiopicrin, palmatine hydrochloride and berberine hydrochloride were 72.8~728?g?mL -1 ( r=0.9998 ), 7.55~75.5?g?mL -1 ( r=0.9998 ), 12.45~124.5?g?mL -1 ( r = 0.9999 ), respectively. The average recoveries ( n =6) of gentiopicrin, palmatine hydrochloride and berberine hydrochloride were 98.17%, 98.78%, 98.60%; RSD were 1.60%, 1.35%, 1.25%, respectively. CONCLUSION: The method is accurate, reproducible and highly selective, thus suitable for quality control of Er Tong Ⅱ Oral Liqual.

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