1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Heterogeneity of Adipose Tissue From a Single-cell Transcriptomics Perspective
Yong-Lang WANG ; Si-Si CHEN ; Qi-Long LI ; Yu GONG ; Xin-Yue DUAN ; Ye-Hui DUAN ; Qiu-Ping GUO ; Feng-Na LI
Progress in Biochemistry and Biophysics 2025;52(4):820-835
Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.
3.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
4.Body Composition Profiles and Associated Factors in Adolescents UndergoingLong-term Regular Exercise
Yutong WANG ; Xiaoyuan GUO ; Hanze DU ; Hui PAN ; Wei WANG ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Hongshuang SUN ; Rong LI ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):591-597
To investigate body composition and associated factors in adolescents undergoing long-term regular sports training. This prospective longitudinal cohort study employed convenience sampling to recruit adolescents receiving structured athletic training at Jining Sports Training Center in June 2023. Baseline measurements included height, weight, body mass index (BMI), blood pressure, heart rate, waist circumference, and hip circumference. Questionnaires assessed sleep duration, screen time, and household income. Follow-up measurements in June 2024 repeated these assessments while adding bioelectrical impedance analysis for body composition (lean mass, skeletal muscle mass, fat mass, and body fat percentage). Linear regression models examined associations between training type (direct-contact vs. non-contact sports) and follow-up body fat percentage, BMI, and waist circumference as dependent variables, adjusting for covariates. The study included 110 adolescents (39 female, 71 male) with median age 13.21 years (IQR: 12.46-14.33). Participants comprised 65 direct-contact and 45 non-contact athletes. Baseline prevalence rates were 27.27% for overweight/obesity, 24.55% for elevated waist circumference, and 16.36% for elevated blood pressure. At follow-up, corresponding rates were 24.55%, 26.36%, and 13.64% respectively. The elevated blood pressure subgroup showed significantly higher waist circumference ( Despite regular athletic training, substantial proportions of adolescents exhibited overweight/obesity, abdominal obesity, and elevated blood pressure, warranting clinical attention. Training modality appears to influence body composition changes, with direct-contact sports associated with more favorable adiposity-related outcomes.
5.Efficacy of Differential Dosage of Pueraria in Gegen Qinliantang on Acute Enteritis Model in Mice
Ruiying ZHANG ; Ping WANG ; Di ZHANG ; Hongfa CHENG ; Ying ZHANG ; Zhu DENG ; Hui FENG ; Min LIU ; Yang TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):197-204
ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis (AE) model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group,model group,single Puerariae Lobatae Radix group,non-Puerariae Lobatae Radix group,regular dose Gegen Qinliantang group (regular dose group),half-dose Puerariae Lobatae Radix group,and doubled-dose Puerariae Lobatae Radix group, with 16 mice in each group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 (a protein in the tight junction) and Occludin in the colon tissue, as well as the changes of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). ResultsCompared with the blank group,the DAI scores of the mice in the model group were significantly higher (P<0.05),and the histopathological sections of their colon tissues showed mucosal damage,glandular atrophy,disordered arrangement,and a large number of inflammatory cells infiltration,and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated (P<0.05,P<0.01). The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated (P<0.05,P<0.01). Compared with the model group,the DAI scores of mice in all dosing groups decreased significantly (P<0.05),with the most significant effect in the regular dose group. After 7 d of drug administration,the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α (P<0.05) and significantly up-regulated the expression of ZO-1 protein (P<0.05). The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein (P<0.01),and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration,the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α (P<0.01). Meanwhile,the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein (P<0.01). The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein (P<0.05) and up-regulated ZO-1 protein expression (P<0.05). ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue, protect the barrier function and structure of intestinal epithelial cells, and reduce the expression of inflammatory factors, so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents, Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.
6.Efficacy of Differential Dosage of Pueraria in Gegen Qinliantang on Acute Enteritis Model in Mice
Ruiying ZHANG ; Ping WANG ; Di ZHANG ; Hongfa CHENG ; Ying ZHANG ; Zhu DENG ; Hui FENG ; Min LIU ; Yang TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):197-204
ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis (AE) model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group,model group,single Puerariae Lobatae Radix group,non-Puerariae Lobatae Radix group,regular dose Gegen Qinliantang group (regular dose group),half-dose Puerariae Lobatae Radix group,and doubled-dose Puerariae Lobatae Radix group, with 16 mice in each group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 (a protein in the tight junction) and Occludin in the colon tissue, as well as the changes of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). ResultsCompared with the blank group,the DAI scores of the mice in the model group were significantly higher (P<0.05),and the histopathological sections of their colon tissues showed mucosal damage,glandular atrophy,disordered arrangement,and a large number of inflammatory cells infiltration,and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated (P<0.05,P<0.01). The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated (P<0.05,P<0.01). Compared with the model group,the DAI scores of mice in all dosing groups decreased significantly (P<0.05),with the most significant effect in the regular dose group. After 7 d of drug administration,the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α (P<0.05) and significantly up-regulated the expression of ZO-1 protein (P<0.05). The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein (P<0.01),and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration,the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α (P<0.01). Meanwhile,the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein (P<0.01). The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein (P<0.05) and up-regulated ZO-1 protein expression (P<0.05). ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue, protect the barrier function and structure of intestinal epithelial cells, and reduce the expression of inflammatory factors, so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents, Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.
7.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
8.Bioequivalence study of buspirone hydrochloride tablets in Chinese healthy subjects
Ping LU ; Rui WANG ; Hui-Hui WU ; Hai-Yan LIU ; Ge-Fei HE ; Shun-Zhi ZHANG ; Wei WU
The Chinese Journal of Clinical Pharmacology 2024;40(5):723-727
Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90%confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00%and 125.00%,and the 95%upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00%and 125.00%.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.
9.Traditional Chinese Medicine Regulates Gut Microbiota in Treatment of Thyroid Diseases via Gut-thyroid Axis: A Review
Shanshan LI ; Dandan WEI ; Yu FU ; Ping WANG ; Hui WANG ; Shuxun YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):254-262
Thyroid diseases are common endocrine disorders with high incidence. The diseases are closely related to genetic factors, immune system disorders, and hormone levels. Although modern medical therapies have achieved certain therapeutic effects, the side effects have affected clinical treatment. In recent years, studies have proven that gut microbiota is a key factor affecting thyroid diseases, and increasing studies have referred to the bidirectional information interaction system between the gut and thyroid as the gut-thyroid axis. This study adopts the meridian-collateral theory and the visceral manifestation theory of traditional Chinese medicine (TCM) to explain the functions, physiological characteristics, and pathological mechanisms of the gut and thyroid. Furthermore, this paper clarifies the mechanism of gut microbiota in modulating thyroid homeostasis by inducing inflammation and altering thyroid hormone metabolism from the perspective of molecular biology, clarifying the rationality of the gut-thyroid axis from the perspectives of TCM and Western medicine. Meanwhile, under the guidance of the gut-thyroid axis, increasing studies have been carried out regarding the application of TCM in regulating gut microbiota in the treatment of thyroid diseases. Both the active component emodin and compound prescription Yiqi Huatan Huoxue prescription of Chinese medicine can treat thyroid diseases by regulating the abundance and diversity of gut microbiota and improving the intestinal mucosal barrier. However, the systematic review of the research on TCM treatment of thyroid diseases by regulating gut microbiota remains to be conducted. This study expounds the gut-thyroid axis from both TCM and Western medicine and reviews the research progress in the TCM treatment of thyroid diseases by regulating gut microbiota, aiming to give new insights into the prevention and treatment of thyroid diseases with TCM.
10.Advances in DNA origami intelligent drug delivery systems
Zeng-lin YIN ; Xi-wei WANG ; Jin-jing CHE ; Nan LIU ; Hui ZHANG ; Zeng-ming WANG ; Jian-chun LI ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2024;59(10):2741-2750
DNA origami is a powerful technique for generating nanostructures with dynamic properties and intelligent controllability. The precise geometric shapes, high programmability, and excellent biocompatibility make DNA origami nanostructures an emerging drug delivery vehicle. The shape, size of the carrier material, as well as the loading and release of drugs are important factors affecting the bioavailability of drugs. This paper focuses on the controllable design of DNA origami nanostructures, efficient drug loading, and intelligent drug release. It summarizes the cutting-edge applications of DNA origami technology in biomedicine, and discusses areas where researchers can contribute to further advancing the clinical application of DNA origami carriers.

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