1.Circulating inflammatory proteins and myocardial hypertrophy:large sample analysis of European populations from GWAS Catalog and FinnGen databases
Yu DING ; Jingwen CHEN ; Xiuyan CHEN ; Huimin SHI ; Yudie YANG ; Meiqi ZHOU ; Shuai CUI
Chinese Journal of Tissue Engineering Research 2026;30(4):1047-1057
BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95%Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95%CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95%CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95%CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95%CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95%CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95%CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.
2.Circulating inflammatory proteins and myocardial hypertrophy:large sample analysis of European populations from GWAS Catalog and FinnGen databases
Yu DING ; Jingwen CHEN ; Xiuyan CHEN ; Huimin SHI ; Yudie YANG ; Meiqi ZHOU ; Shuai CUI
Chinese Journal of Tissue Engineering Research 2026;30(4):1047-1057
BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95%Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95%CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95%CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95%CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95%CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95%CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95%CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.
3.Disease burden and trend prediction of autism spectrum disorder in children and adolescents in China and globally
GAO Yue, LI Hongjie, CHEN Meiqi, ZHOU Yang, YANG Xiaolei
Chinese Journal of School Health 2026;47(2):268-272
Objective:
To analyze the current burden of autism spectrum disorder (ASD) among children and adolescents in China and globally, and to predict the disease burden from 2024 to 2035, providing a scientific basis for formulating relevant public health policies and intervention measures.
Methods:
Based on the Global Burden of Disease (GBD) database in 2023, the Joinpoint regression model was used to analyze the changing trends of the disease burden of ASD among children and adolescents in China and globally from 1990 to 2023, and the average annual percent change (AAPC) was calculated. An autoregressive integrated moving average (ARIMA) model was constructed to predict the disease burden trends of ASD among children and adolescents in China and globally from 2024 to 2035.
Results:
The prevalence and disability adjusted life years (DALYs) rate of ASD among children and adolescents in China increased from 452.69/100 000 and 86.67/100 000 in 1990 to 762.84/100 000 and 148.52/ 100 000 in 2023(AAPC=1.60%, 1.65%, both P <0.01). The prevalence and DALYs rate of ASD among children and adolescents globally increased from 648.49/100 000 and 123.47/100 000 to 862.44/100 000 and 167.16/100 000(AAPC=0.87%, 0.93%, both P <0.01). In 2023, the highest ASD prevalence and DALY rates occurred in children under 5 years old, with China reporting 848.14/100 000 and 166.69/100 000, both below the global averages of 928.80/100 000 and 181.34/100 000. Projections indicated that by 2035, the ASD prevalence and DALY rates in China would rise to 906.83/100 000 and 168.71/100 000, still below the global averages of 938.04/100 000 and 184.49/100 000.
Conclusion
The disease burden of ASD among children and adolescents in China and globally has generally increased from 1990 to 2023, with a higher risk of disease at younger ages.
4.Proanthocyanidins regulate retinal autophagy in form-deprivation myopic guinea pigs through the AMPK/Wnt/β-catenin pathway
Jifu LIU ; Xiaotian YANG ; Bowen ZHENG ; Chen YE ; Meiqi FANG
International Eye Science 2025;25(12):1906-1913
AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.
5.Effects of sialic acid intervention on intestinal function in autism model rats
Chao YANG ; Hongjie LI ; Gang LI ; Yue GAO ; Meiqi CHEN ; Xiaolei YANG
Chinese Journal of Comparative Medicine 2025;35(10):20-27
Objective To explore the effects of sialic acid intervention during pregnancy and the lactational period on the intestinal function of autism model rats.Methods Thirty SPF-grade adult male and female Wistar rats were mated.The successfully pregnant rats were randomly assigned to a valproate-induced model(VPA)group,a high-dose sialic acid(SAH)group,a medium-dose sialic acid(SAM)group,a low-dose sialic acid(SAL)group,and a control(CON)group(n=6 per group)and were housed individually in single cages.On the 12.5th day of pregnancy(E12.5),rats in the VPA and SA intervention groups were given a single intraperitoneal injection of 600 mg/kg sodium valproate(VPA),while the pregnant rats in the CON group were given an equal amount of normal saline.The SA intervention period was from E12.5 to the 21st day after parturition.Feces of offspring rats in each group were collected.The diversity and structure of the gut microbiota were detected by 16S rRNA sequencing.The intestinal transit speed in each group was detected by intragastric administration of carmine.The levels of intestinal-related neurotransmitters(substance P,enkephalin,5-hydroxytryptamine,vasoactive intestinal peptide,and glutamate,gamma-aminobutyric acid)in the blood of rats in each group were detected by ELISA.Results High-dose SA intervention did not affect the diversity of the gut microbiota in the VPA-induced autism model rats,but it changed the structure of the gut microbiota and increased the abundance levels of Prevotella_NK3B31 group,Prevotella,Prevotella spp.,Alloprevotella,Lachnospira,Ruminococcus,and Bacteroides(P<0.05).High-dose SA also promoted the intestinal transit speed,and increased the levels of vasoactive intestinal peptide,5-hydroxytryptamine,and gamma-aminobutyric acid in serum.Conclusions SA intervention during pregnancy and the lactational period affects the intestinal transit speed of VPA-induced autism model rats,changes the structure of the gut microbiome,and increases the levels of vasoactive intestinal peptide,5-hydroxytryptamine,and gamma-aminobutyric acid.
6.Role of umbilical cord mesenchymal stem cell-derived nanovesicles in inducing hair regeneration
Yuxin DING ; Yujie MIAO ; Meiqi MAO ; Jinyang CHEN ; Zhiwei LIN ; Zhongfa LYU
Chinese Journal of Dermatology 2025;58(5):431-439
Objective:To investigate the role of umbilical cord mesenchymal stem cell (MSC) -derived nanovesicles in hair regeneration.Methods:(1) Nanovesicles were prepared by continuously extruding umbilical cord MSCs through polycarbonate membranes, and were identified using transmission electron microscopy and nanoparticle tracking analysis. (2) Six C57BL/6 female mice with full-thickness skin wounds were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles once at the wound margin) and a control group (subcutaneously injected with an equal volume of phosphate-buffered saline [PBS] at the wound margin) ; skin samples were collected on day 16 for hematoxylin-eosin (HE) staining to assess wound healing and hair follicle regeneration. (3) Human hair follicle dermal papilla cells (DPCs) were isolated using a two-step enzyme method; the uptake of PKH26-pre-labeled nanovesicles by DPCs was observed by fluorescence microscopy; the proliferative activity of DPCs co-cultured with nanovesicles was evaluated using cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. (4) Six healthy C57BL/6 female mice were randomly divided into two groups after anesthesia, and subcutaneously injected with either fluorescent dye DIR-pre-labeled nanovesicles or PBS; an in vivo imaging system was used to observe the uptake and metabolism of nanovesicles in the mouse skin. (5) Twenty-four C57BL/6 female mice with depilated backs were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles on days 0, 8, and 15) and a control group (subcutaneously injected with an equal volume of PBS at the same time points) ; skin samples were collected on days 4, 18, and 21 for HE staining to analyze differences in hair follicle cycling; transcriptome sequencing was performed on skin samples collected on day 4. Statistical analyses were conducted using the t test. Results:(1) Transmission electron microscopy showed that nanovesicles exhibited a spherical membranous structure with diameters of 141.3 ± 60.0 nm. (2) In 6 C57BL/6 female mice with full-thickness skin wounds, the wound area on day 12 was significantly smaller in the nanovesicle group (1.27 ± 0.50 mm 2) than in the control group (4.13 ± 1.03 mm 2, t = 4.34, P = 0.012). (3) Fluorescence microscopy revealed that nanovesicles were taken up by DPCs within 20 hours; the absorbance of DPCs was significantly higher in the nanovesicle group than in the control group ( t = 20.23, P < 0.001), and the percentage of EdU-positive cells was also significantly higher in the nanovesicle group (49.62% ± 6.45%) than in the control group (37.58% ± 3.42%, t = 3.69, P = 0.006). (4) In vivo imaging of the 6 C57BL/6 female mice showed strong fluorescence in the back of mice in the nanovesicle group on day 0, which markedly decreased by day 8, while no fluorescence was observed in the control group throughout the experiment. (5) Hair follicle cycle experiments on the 24 C57BL/6 female mice with depilated backs showed that the hair follicle length on day 4 after depilation was significantly longer in the nanovesicle group (368.00 ± 63.17 μm) than in the control group (266.90 ± 34.41 μm, t = 9.87, P < 0.001), and the hair bulb diameter was also significantly longer in the nanovesicle group (54.83 ± 10.32 μm) than in the control group (39.12 ± 7.54 μm, t = 16.02, P < 0.001) ; on day 18, the nanovesicle group showed a significantly higher hair follicle density (19.12 ± 0.90) compared with the control group (11.07 ± 1.51, t = 7.92, P = 0.001) ; on day 21, 46.13% ± 8.64% of hair follicles in the nanovesicle group remained in the anagen phase Ⅵ to the catagen phase Ⅱ, and 46.24% ± 3.29% were in the catagen phases Ⅲ to Ⅳ, while 78.89% ± 18.36% of hair follicles in the control group were in the telogen phases Ⅶ to Ⅷ. Transcriptome sequencing showed that differentially expressed genes in the nanovesicle group were significantly positively enriched in the keratinization process (NES = 2.23, P < 0.001) . Conclusion:Umbilical cord MSC-derived nanovesicles could promote the proliferation of DPCs, advance the entry of hair follicles into the anagen phase, delay their entry into the catagen phase, and induce hair regeneration.
7.A network meta-analysis on the efficacy and mechanism of traditional Chinese medicine combined with mesalazine in the treatment of ulcerative colitis
Fan ZHANG ; Xuan ZHOU ; Hongmin ZHUO ; Yan CHEN ; Baoping REN ; Meiqi ZHONG ; Meiyan ZENG ; Houpan SONG
Chongqing Medicine 2025;54(6):1408-1418
Objective To evaluate the efficacy and safety of six kinds of commonly used traditional Chi-nese medicine combined with mesalazine in the treatment of ulcerative colitis(UC)based on frequency statis-tical network meta-analysis.Methods Randomized controlled trials(RCT)of oral Chinese medicine for the treatment of UC were searched from the establishment of the database to June 2024 of PubMed,CNKI,Wan-fang,VIP,Sinomed and other databases.The quality of the included literatures was evaluated by Cochrane bias risk assessment tool,and the data were statistically analyzed by Stata MP17.0 software.Results A total of 24 RCTs involving 1 939 patients were included,involving 6 kinds of traditional Chinese medicine and Chinese pa-tent medicine,including 4 macro and micro outcome indicators.In terms of improving the total clinical effec-tive rate,Shaoyao decoction,Gancao Xiexin decoction,Huangqin decoction granule,Baitouweng decoction,Kangfuxin liquid,Shenlingbaizhu powder+mesalazine were all superior to using mesalazine alone,and Kang-fuxin liquid+mesalazine had the best effect(P<0.05).In terms of down-regulation of interleukin(IL)-6 expression in colonic mucosa,Shaoyao decoction,Gancao Xiexin Decoction,Huangqin Decoction granules,Pul-satilla decoction,Kangfuxin Liquid+mesalazine were better than using mesalazine alone,and Pulsatilla De-coction+mesalazine had the best effect on reducing IL-6(P<0.05).In terms of down-regulation of colonic mucosal tumor necrosis factor(TNF)-α expression,Shaoyao decoction,Gancao Xiexin decoction,Huangqin decoction granule,Baitouweng decoction,Shenlingbaizhu decoction+mesalazine was better than using me-salazine alone,and Gancao Xiexin decoction+mesalazine had the best effect(P<0.05).In terms of down-regulation of IL-10 expression in colonic mucosa,Pulsatilla decoction+mesalazine was better than mesalazine alone(P<0.05).Conclusion Traditional Chinese medicine combined with mesalazine could alleviate the clin-ical symptoms of UC patients,improve inflammatory factor indicators,eliminate inflammation,and show a better treatment effect for UC than mesalazine used alone.
8.A preliminary exploration of an intelligent system for personalized tooth morphology reconstruction based on deep learning
Meiqi YU ; Du CHEN ; Zhenyu WANG ; Fei LIU ; Yanyan ZHANG ; Yunpeng LI ; Jiefei SHEN
Chinese Journal of Stomatology 2025;60(6):618-625
Objective:To integrate implicit templates with deep learning techniques, a novel neural network, the tooth-deformable deep implicit network (T-DDIN), was constructed to achieve high-precision shape completion of tooth defects in a personalized manner.Methods:A total of 550 intraoral scan models were collected from patients treated at the Department of Orthodontics and Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University (500 for training and 50 for testing), between March 2022 and March 2024. T-DDIN reconstructed defective tooth morphology using an implicit template and a latent encoding prediction network. During model evaluation, Class Ⅱ cavity defects and occlusal wear defects were simulated in the test set. Morphological restoration was performed using both traditional computer aided design (CAD) methods and the T-DDIN deep learning approach. The two methods were compared based on three-dimensional deviation, occlusal adjustment volumes, cusp angle deviation, and restoration time.Results:The T-DDIN group demonstrated significantly lower three-dimensional deviation for Class Ⅱ cavity defects and occlusal wear restoration [(0.14±0.05) and (0.16±0.09) mm], occlusal adjustment volumes [(0.44±0.03) and (0.49±0.03) mm 3], and difference value of the tooth cusp angles (5.69°±1.90° and 6.04°±0.53°) compared to the traditional CAD group (both P<0.001). No significant differences were observed within the T-DDIN group between the two defect types in terms of three-dimensional deviation ( P=0.098) or occlusal adjustment volume ( P=0.154) or difference value of the tooth cusp angles ( P=0.196). However, in the traditional CAD group, three-dimensional deviation, occlusal adjustment volume and difference value of the tooth cusp angles was significantly higher in occlusal wear restorations than in Class Ⅱ cavity defects restorations ( P<0.001). The T-DDIN group, which involved Class Ⅱ cavity defects and occlusal wear, demonstrated significantly less recovery time of morphology (37.2±7.7) and (39.4±6.2) s compared to the traditional CAD group ( P<0.001). Conclusions:T-DDIN demonstrated superior stability and accuracy in morphological reconstruction for various types of dental defects while significantly reducing restoration time.
9.Role of umbilical cord mesenchymal stem cell-derived nanovesicles in inducing hair regeneration
Yuxin DING ; Yujie MIAO ; Meiqi MAO ; Jinyang CHEN ; Zhiwei LIN ; Zhongfa LYU
Chinese Journal of Dermatology 2025;58(5):431-439
Objective:To investigate the role of umbilical cord mesenchymal stem cell (MSC) -derived nanovesicles in hair regeneration.Methods:(1) Nanovesicles were prepared by continuously extruding umbilical cord MSCs through polycarbonate membranes, and were identified using transmission electron microscopy and nanoparticle tracking analysis. (2) Six C57BL/6 female mice with full-thickness skin wounds were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles once at the wound margin) and a control group (subcutaneously injected with an equal volume of phosphate-buffered saline [PBS] at the wound margin) ; skin samples were collected on day 16 for hematoxylin-eosin (HE) staining to assess wound healing and hair follicle regeneration. (3) Human hair follicle dermal papilla cells (DPCs) were isolated using a two-step enzyme method; the uptake of PKH26-pre-labeled nanovesicles by DPCs was observed by fluorescence microscopy; the proliferative activity of DPCs co-cultured with nanovesicles was evaluated using cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. (4) Six healthy C57BL/6 female mice were randomly divided into two groups after anesthesia, and subcutaneously injected with either fluorescent dye DIR-pre-labeled nanovesicles or PBS; an in vivo imaging system was used to observe the uptake and metabolism of nanovesicles in the mouse skin. (5) Twenty-four C57BL/6 female mice with depilated backs were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles on days 0, 8, and 15) and a control group (subcutaneously injected with an equal volume of PBS at the same time points) ; skin samples were collected on days 4, 18, and 21 for HE staining to analyze differences in hair follicle cycling; transcriptome sequencing was performed on skin samples collected on day 4. Statistical analyses were conducted using the t test. Results:(1) Transmission electron microscopy showed that nanovesicles exhibited a spherical membranous structure with diameters of 141.3 ± 60.0 nm. (2) In 6 C57BL/6 female mice with full-thickness skin wounds, the wound area on day 12 was significantly smaller in the nanovesicle group (1.27 ± 0.50 mm 2) than in the control group (4.13 ± 1.03 mm 2, t = 4.34, P = 0.012). (3) Fluorescence microscopy revealed that nanovesicles were taken up by DPCs within 20 hours; the absorbance of DPCs was significantly higher in the nanovesicle group than in the control group ( t = 20.23, P < 0.001), and the percentage of EdU-positive cells was also significantly higher in the nanovesicle group (49.62% ± 6.45%) than in the control group (37.58% ± 3.42%, t = 3.69, P = 0.006). (4) In vivo imaging of the 6 C57BL/6 female mice showed strong fluorescence in the back of mice in the nanovesicle group on day 0, which markedly decreased by day 8, while no fluorescence was observed in the control group throughout the experiment. (5) Hair follicle cycle experiments on the 24 C57BL/6 female mice with depilated backs showed that the hair follicle length on day 4 after depilation was significantly longer in the nanovesicle group (368.00 ± 63.17 μm) than in the control group (266.90 ± 34.41 μm, t = 9.87, P < 0.001), and the hair bulb diameter was also significantly longer in the nanovesicle group (54.83 ± 10.32 μm) than in the control group (39.12 ± 7.54 μm, t = 16.02, P < 0.001) ; on day 18, the nanovesicle group showed a significantly higher hair follicle density (19.12 ± 0.90) compared with the control group (11.07 ± 1.51, t = 7.92, P = 0.001) ; on day 21, 46.13% ± 8.64% of hair follicles in the nanovesicle group remained in the anagen phase Ⅵ to the catagen phase Ⅱ, and 46.24% ± 3.29% were in the catagen phases Ⅲ to Ⅳ, while 78.89% ± 18.36% of hair follicles in the control group were in the telogen phases Ⅶ to Ⅷ. Transcriptome sequencing showed that differentially expressed genes in the nanovesicle group were significantly positively enriched in the keratinization process (NES = 2.23, P < 0.001) . Conclusion:Umbilical cord MSC-derived nanovesicles could promote the proliferation of DPCs, advance the entry of hair follicles into the anagen phase, delay their entry into the catagen phase, and induce hair regeneration.
10.Effects of sialic acid intervention on intestinal function in autism model rats
Chao YANG ; Hongjie LI ; Gang LI ; Yue GAO ; Meiqi CHEN ; Xiaolei YANG
Chinese Journal of Comparative Medicine 2025;35(10):20-27
Objective To explore the effects of sialic acid intervention during pregnancy and the lactational period on the intestinal function of autism model rats.Methods Thirty SPF-grade adult male and female Wistar rats were mated.The successfully pregnant rats were randomly assigned to a valproate-induced model(VPA)group,a high-dose sialic acid(SAH)group,a medium-dose sialic acid(SAM)group,a low-dose sialic acid(SAL)group,and a control(CON)group(n=6 per group)and were housed individually in single cages.On the 12.5th day of pregnancy(E12.5),rats in the VPA and SA intervention groups were given a single intraperitoneal injection of 600 mg/kg sodium valproate(VPA),while the pregnant rats in the CON group were given an equal amount of normal saline.The SA intervention period was from E12.5 to the 21st day after parturition.Feces of offspring rats in each group were collected.The diversity and structure of the gut microbiota were detected by 16S rRNA sequencing.The intestinal transit speed in each group was detected by intragastric administration of carmine.The levels of intestinal-related neurotransmitters(substance P,enkephalin,5-hydroxytryptamine,vasoactive intestinal peptide,and glutamate,gamma-aminobutyric acid)in the blood of rats in each group were detected by ELISA.Results High-dose SA intervention did not affect the diversity of the gut microbiota in the VPA-induced autism model rats,but it changed the structure of the gut microbiota and increased the abundance levels of Prevotella_NK3B31 group,Prevotella,Prevotella spp.,Alloprevotella,Lachnospira,Ruminococcus,and Bacteroides(P<0.05).High-dose SA also promoted the intestinal transit speed,and increased the levels of vasoactive intestinal peptide,5-hydroxytryptamine,and gamma-aminobutyric acid in serum.Conclusions SA intervention during pregnancy and the lactational period affects the intestinal transit speed of VPA-induced autism model rats,changes the structure of the gut microbiome,and increases the levels of vasoactive intestinal peptide,5-hydroxytryptamine,and gamma-aminobutyric acid.


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