1.Kynurenine Pathway and Its Metabolites in Autism Spectrum Disorder: a Close Link
Ya-Qian XIAO ; Li-Chen QIAO ; De-Chang RONG ; Yu-Chen LEI ; Hakan ÜREY ; Lan-Lan ZUO ; Hasan BAYRAM ; Reza A. GHILADI ; Yi-Fan DUAN ; Meng-Jiao LI
Progress in Biochemistry and Biophysics 2026;53(9):2402-2413
Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.
2.Study of Reference Materials for Quantitative Analysis of Gene Copy Numbers of Lentiviral Vectors
Yin-Bo HUO ; Jia-Qi YANG ; Qing TAO ; Wen LIANG ; Li XU ; Lan-Ying LI ; Xiao-Lei ZUO ; Juan YAN ; Min DING ; Ai-Wen MA ; Gang LIU
Chinese Journal of Analytical Chemistry 2025;53(9):1555-1565
Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.
3.Effects of Modified Baitouweng Decoction and Lizhong Decoction on the improvement of mouse ulcerative colitis through autophagy regulation via AMPK/mTOR/p70S6K signaling pathway
Ya-fen ZHANG ; Zhen-kui ZUO ; Hong-lei JIAN ; Lin WANG ; Tian-rui LIU ; Lan-xin REN
Chinese Traditional Patent Medicine 2025;47(7):2198-2205
AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3%dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P<0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P<0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P<0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P<0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.
4.Change Law in Material Basis of Rhei Radix et Rhizoma During Nine-time Repeating Steaming and Sun-drying Processing Based on Characteristic Chromatogram and Chemometrics
Xuan AO ; Taotao LIU ; Miao YU ; Lan WANG ; Xiaojie YIN ; Jingyu ZUO ; Li LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):191-198
ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma, and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography(HPLC) was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces, and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside, chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics, the contents and quantity ratio relationships of the glycosides, aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed, and the partial least squares-discriminant analysis(PLS-DA) and cluster analysis of the main components in different steaming times were conducted, the statistically significant differential markers were selected with the variable importance in the projection(VIP) value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma, there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times, the anthraquinone glycosides and aglycones could be roughly divided into three stages, including rapid change stage, fluctuation change stage and stable stage, and the total amount of tannins showed a decreasing trend. However, the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes, while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening, it was found that chrysophanol, emodin, chrysophanol-8-O-β-D-glucoside, rhein, physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb, which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.
5.Recent advance in role of non-invasive brain stimulation in Alzheimer's disease
Yuankai WANG ; Yufei LAN ; Feiyunduo HAO ; Manqing ZHANG ; Lei LI ; Boming ZUO ; Yang LI ; Xinyun XIE ; Hongbo GUO
Chinese Journal of Neuromedicine 2025;24(2):193-200
Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease, which has become the leading cause of dementia in the elderly. In recent years, non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation, transcranial electrical stimulation, focused ultrasound stimulation and transcranial photobiomodulation, has been widely used in AD treatment. Although NIBS can improve the clinical symptoms of AD patients, its efficacy is still controversial. This article reviews the latest research progress in role of NIBS in AD so as to provide reference for clinical workers.
6.Preliminary study on hearing screening for the elderly population undergoing physical examinations
Jianglan ZUO ; Yanan LAN ; Wen SUN ; Yufei QIAO ; Jing LI ; Yingying SHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(2):166-171
Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.
7.Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum.
Xue ZHANG ; Jing HAN ; Yudong WANG ; Li FENG ; Zhisong FAN ; Yu SU ; Wenya SONG ; Lan WANG ; Long WANG ; Hui JIN ; Jiayin LIU ; Dan LI ; Guiying LI ; Yan LIU ; Jing ZUO ; Zhiyu NI
Protein & Cell 2025;16(6):491-496
8.Effects of Modified Baitouweng Decoction and Lizhong Decoction on the improvement of mouse ulcerative colitis through autophagy regulation via AMPK/mTOR/p70S6K signaling pathway
Ya-fen ZHANG ; Zhen-kui ZUO ; Hong-lei JIAN ; Lin WANG ; Tian-rui LIU ; Lan-xin REN
Chinese Traditional Patent Medicine 2025;47(7):2198-2205
AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3%dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P<0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P<0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P<0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P<0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.
9.Recent advance in role of non-invasive brain stimulation in Alzheimer's disease
Yuankai WANG ; Yufei LAN ; Feiyunduo HAO ; Manqing ZHANG ; Lei LI ; Boming ZUO ; Yang LI ; Xinyun XIE ; Hongbo GUO
Chinese Journal of Neuromedicine 2025;24(2):193-200
Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease, which has become the leading cause of dementia in the elderly. In recent years, non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation, transcranial electrical stimulation, focused ultrasound stimulation and transcranial photobiomodulation, has been widely used in AD treatment. Although NIBS can improve the clinical symptoms of AD patients, its efficacy is still controversial. This article reviews the latest research progress in role of NIBS in AD so as to provide reference for clinical workers.
10.Preliminary study on hearing screening for the elderly population undergoing physical examinations
Jianglan ZUO ; Yanan LAN ; Wen SUN ; Yufei QIAO ; Jing LI ; Yingying SHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(2):166-171
Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

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