1.Mechanism of Wenyang jieyu granules regulating NLRP3/ASC/Caspase-1 pathway on antidepressant effect in rats
Shuang MENG ; Jie ZHAO ; Xinxin WANG ; Dandan TAN ; Xiaorong ZHOU ; Huimin SUN ; Xiaojuan MA ; Zhenyu FENG
China Pharmacy 2026;37(11):1440-1446
OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules (WYJYG) via the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a CARD (ASC)/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group, model group, MCC950 (NLRP3 inflammasome inhibitor) group (10 mg/kg), fluoxetine group (positive control,2.08 mg/kg),low-dose WYJYG(3.78 g/kg) and high-dose WYJYG group (7.56 g/kg),with 10 rats in each group. From the 22nd day of the experiment, rats in the fluoxetine group, low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration, the contents of ASC, ionized calcium binding adaptor molecule 1 (Iba1), interleukin-1β (IL-1β), and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3, cluster of differentiation 68 (CD68), Caspase-1, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein were determined, and neuronal apoptosis was observed. RESULTS After the last administration, compared with the model group, the open-field activity time was significantly prolonged ( P <0.05), and the latency to feed in a novel environment was significantly shortened ( P <0.05) in rats of the high-dose WYJYG group. In hippocampal tissue, the contents of ASC, Iba1, IL-1β, and IL-18, as well as the protein expression levels of NLRP3, Caspase-1, and CD68, and the positive rate of neuronal apoptosis were all significantly decreased/downregulated ( P <0.05). Bcl-2 protein expression was significantly upregulated ( P <0.05), and the density of neuronal apoptosis-positive cells was significantly reduced ( P <0.05). CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway, reducing microglia-mediated neuroinflammation, and inhibiting hippocampal neurons apoptosis.
2.Modified probiotics and the related combinatorial therapeutics.
Luo ZHAO ; Mengya NIU ; Zilin MA ; Fengyun HE ; Xinxin LIU ; Xunwei GONG ; Zhanfei CHAI ; Ziqing WANG ; Qianhua FENG ; Lei WANG
Acta Pharmaceutica Sinica B 2025;15(5):2431-2453
Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.
3.Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m6A modification of calsequestrin 2 in diabetic cardiomyopathy.
Xiaohan LI ; Ling LIU ; Han LOU ; Xinxin DONG ; Shengxin HAO ; Zeqi SUN ; Zijia DOU ; Huimin LI ; Wenjie ZHAO ; Xiuxiu SUN ; Xin LIU ; Yong ZHANG ; Baofeng YANG
Frontiers of Medicine 2025;19(2):329-346
Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca2+ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca2+ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m6A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca2+ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals
;
Diabetic Cardiomyopathies/pathology*
;
RNA, Long Noncoding/genetics*
;
Myocytes, Cardiac/metabolism*
;
Mice
;
Calsequestrin/genetics*
;
Calcium/metabolism*
;
Male
;
Sarcoplasmic Reticulum/metabolism*
;
Methyltransferases/metabolism*
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Mice, Inbred C57BL
;
Mitochondria, Heart/metabolism*
;
Disease Models, Animal
;
Mitochondria/metabolism*
4.Screening of soil biocontrol bacteria and evaluation of their control effects on Fusarium head blight of wheat.
Dongfang WANG ; Xinxin ZHAI ; Chunlin YANG ; Huilan ZHANG ; Jie WU ; Zerong SONG ; Pan ZHAO ; Yu CHI
Chinese Journal of Biotechnology 2025;41(10):3764-3773
Fusarium head blight (FHB), caused by Fusarium graminearum, not only leads to severe yield losses but also poses a threat to food safety due to the mycotoxins produced by the pathogen. Since this disease is preventable but not curable, the current control mainly relies on chemical fungicides, the long-term use of which may lead to pathogen resistance and environmental pollution. To develop green control methods, we screened 13 biocontrol strains from the rhizosphere soil of wheat, among which strain No. 12 (identified as Pythium aphanidermatum) showed significant antifungal effects. In the plate confrontation test, this strain reduced the colony diameter of the pathogen by 69.2% (1.47 mm vs. 4.78 mm in the control group), with an inhibition rate of 77% (P < 0.01). Microscopic observation revealed obvious deformations in the pathogen hyphae, suggesting a lysing effect. The coleoptile experiment further confirmed that the pre-treatment with this strain reduced the incidence rate to 0. These findings provide new candidate strains for the biocontrol of FHB and offer a scientific basis for reducing the use of chemical fungicides and promoting sustainable agricultural development.
Triticum/growth & development*
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Fusarium/growth & development*
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Plant Diseases/prevention & control*
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Soil Microbiology
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Pest Control, Biological/methods*
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Pythium/physiology*
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Biological Control Agents
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Rhizosphere
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Fungicides, Industrial
5.Overview of the Research on Mechanisms and Application of Essential Oil of Aromatic Chinese Medicinals in Prevention of Respiratory Infectious Disease
Wan Ling LI ; Xinxin WU ; Xiaolei LI ; Mingzhao HAO ; Fang ZHANG ; Yue ZHANG ; Haoyue LI ; Jing ZHAO
Journal of Traditional Chinese Medicine 2025;66(6):638-644
Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs, which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition, immune regulation, and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation, smearing, topical application, bathing, gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification, through methods like diffusion, vaporization, or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience, quick absorption, and simultaneous influence on both the body and mind. However, there are still challenges and deficiencies in aspects such as the positioning of functions, indications, safety, and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils, and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation, and prevent and treat respiratory infectious diseases efficiently, accurately, and safely, thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.
6.A multidimensional analysis of the UK students mental health assessment system and implications
Chinese Journal of School Health 2025;46(4):460-464
Abstract
The mental health assessment work for students in the UK is based on mental health promotion theory, employing a multidimensional approach to evaluate emotional disorders, conduct disorders, hyperactivity disorders, and other aspects across the entire educational continuum from preschool to university. Utilizing international validated standardized scales and customized questionnaires, the system has demonstrated significant preventive efficacy against student mental health issues. China stands to gain valuable insights from the UKs experience, particularly in implementing the Special Action Plan for Comprehensively Strengthening and Improving Students Mental Health Work in the New Era (2023-2025). Strategic adaptation could involve expanding assessment populations, refining evaluation criteria, standardizing measurement tools, and strengthening implementation protocols to systematically enhance Chinas students mental health assessment framework.
7.Association between abdominal fat parameters derived from quantitative CT and coronary artery calcification in middle-aged and elderly adults
Yaqing LI ; Li LI ; Xinxin JIANG ; Wenqi BAI ; Mengyao WANG ; Yanan ZHAO ; Weijun QIAN
Chinese Journal of General Practitioners 2025;24(9):1136-1142
Objective:To investigate the association between abdominal fat-related indicators derived from quantitative computed tomography (QCT) and coronary artery calcification (CAC) in middle-aged and elderly individuals, as well as the diagnostic value of these indicators.Methods:This cross-sectional study enrolled middle-aged and elderly participants who underwent health check-ups at Kaifeng Central Hospital between January and December 2024. Participants were divided into a CAC group and a non-CAC group based on the presence or absence of CAC. The CAC group was then stratified into mild, moderate, and severe subgroups according to CAC severity. General clinical data were collected for all participants. All subjects underwent one-stop QCT scanning of the chest and abdomen. An automated abdominal fat analysis system was used to identify fat distribution regions. If accurate identification was not possible, a semi-automated segmentation algorithm combined with manual correction was applied instead. Two physicians performed the measurements independently, and inter-observer consistency was assessed. The average values were calculated to obtain visceral fat area (VFA) and subcutaneous fat area (SFA). The ratio of visceral fat area to subcutaneous fat area (VFA/SFA) was also computed. Multivariate logistic regression analysis was performed to identify the factors associated with CAC in middle-aged and elderly individuals. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of these indicators for CAC. DeLong′s test was used to compare the differences in the area under the curve ( AUC). Results:A total of 252 middle-aged and elderly individuals were included, with a median age of 61 (interquartile rang: 59, 69) years. Of these individuals, 188(74.6%) were males. Among them, 172 were classified into the CAC group and 80 into the non-CAC group. Multivariate logistic regression analysis revealed that VFA, VFA/SFA ratio, age, low-density lipoprotein cholesterol(LDL-C), and hypertension were independently associated with CAC in middle-aged and elderly individuals (all P<0.05). The mild, moderate, and severe CAC subgroups comprised 78, 51, and 43 participants, respectively. Analysis of variance (ANOVA) demonstrated that VFA and VFA/SFA increased with CAC severity, and there were statistically significant differences between the subgroups (all P<0.05). ROC curve analysis showed that the AUCs of VFA and VFA/SFA for diagnosing CAC were 0.841 and 0.810, respectively, with no significant difference between them ( P>0.05). The optimal cutoff values were 177.45 cm2 for VFA (sensitivity: 83.1%, specificity: 72.5%) and 1.592 for VFA/SFA (sensitivity: 65.7%, specificity: 83.7%). For the diagnosis of moderate-to-severe CAC, the AUCs of VFA and VFA/SFA were 0.765 and 0.761, respectively ( P>0.05 for comparison), with cutoff values of 231.75 cm2 (sensitivity: 61.7%, specificity: 83.3%) and 1.962 (sensitivity: 64.9%, specificity: 80.8%). Conclusion:Abdominal VFA and VFA/SFA derived from QCT are independently associated with the presence of CAC in middle-aged and elderly individuals, demonstrating good diagnostic performance for both overall CAC and moderate-to-severe CAC.
8.Construction, breeding, and gene identification of TREM2 knockout mice
Rong Huang ; Xinxin Zhao ; Hui Xue ; Mengjuan Zhu ; Jiajie Tu ; Xinming Wang
Acta Universitatis Medicinalis Anhui 2025;60(6):977-983
Objective :
To construct triggering receptor expressed on myeloid cells 2(TREM2) gene knockout(TREM2-/-) mice using CRISPR/Cas9 technology, to breed TREM2-/- mice and to analyze the genotype of TREM2-/- mice.
Methods :
CRISPR/Cas9 technology was used to selectively knock out exon 2-3 regions of TREM2 gene to construct a TREM2-/- mouse model, and the genetic background of all mice was C57BL/6J. Polymerase chain reaction(PCR) was used to identify the genotype of mice. Quantitative real-time PCR(qPCR) and Western blot were used to detect the expression level of TREM2 in major tissues of mice, and the authenticity and scientific nature of PCR identification results were verified from mRNA level and protein level. According to the sgRNA sequence, the possible off-target sites were predicted on the CCTop website, and the tail DNA of mice was extracted and amplified by PCR and then Sanger sequencing was performed to detect whether there was off-target effect in TREM2-/- mice.
Results :
TREM2-/- mice were successfully constructed by CRISPR/Cas9 technology, and the mice were genotyped. The results of agarose gel electrophoresis showed that the mouse genotype with only 415 bp band amplified was wild type(WT), the mouse genotype of the 449 bp band amplified only was TREM2-/-, and the mouse genotypes amplified with 415 bp and 449 bp double bands were heterozygous. qPCR results showed that compared with WT mice, the mRNA expression of TREM2 in heart and brain tissues of TREM2-/- mice was down-regulated(P-/- mice was reduced(P-/- mice.
Conclusion
TREM2-/- mice are successfully constructed and bred, a reliable genotype identification method is established, the genetic stability of the mouse model is verified, which will provide an important genetic animal model for the study of TREM2 gene function.
9.Research progress in mechanism of podocyte injury and its potential therapeutic strategies for diabetic nephropathy
Xun LU ; Chengxin MA ; Jianan YANG ; Xinxin GUO ; Xiaobei XIE ; Binghai ZHAO ; Hongzhi LI
Journal of Jilin University(Medicine Edition) 2025;51(5):1415-1422
Diabetic nephropathy(DN)is a significant causative factor of end-stage renal disease globally,and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways.Podocytes play crucial roles in the process of DN,with the extent of podocyte injury closely associated with key pathological manifestations of renal damage,such as proteinuria,glomerular filtration rate,and glomerulosclerosis.However,due to the complexity and interplay of mechanisms contributing to podocyte injury,such as oxidative stress,abnormal lipid metabolism,and mitochondrial damage,the precise mechanisms underlying podocyte injury remain incompletely understood.This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN.Furthermore,this article summarized the implications of these mechanisms for DN treatment,particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways,so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.
10.Exploration on the development of TCM in Central and Eastern Europe
Xinxin WU ; Haoyue LI ; Xiaolei LI ; Yue ZHANG ; Jing ZHAO
International Journal of Traditional Chinese Medicine 2025;47(1):18-22
With the deepening of the "Belt and Road" initiative, Central and Eastern Europe (CEE) presents new opportunities for the development of TCM. In recent years, CEE countries have made some progress in TCM by expanding legislation, establishing educational systems, and diversifying services. These advancements are attributed to cultural recognition, evolving health concepts, and government support. However, challenges persist in sustainability, legal adaptability, and a shortage of professional talents. To effectively tackle these challenges, this article proposed the following suggestions: gradual integration, initial implementation of non-pharmaceutical therapy-centered TCM health services to address legal adaptation issues; empowering with technology to alleviate talent shortage by launching remote medical service models; tailoring measures to local conditions and promote the sustainable development of the TCM industry by integrating regional characteristics; thereby promoting the robust development of TCM in the CEE regions.


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