1.KDM5A/cGAS-STING–mediated microglial activation contributes to prenatal fine particulate matter induced cerebral cortical injury in offspring mice
Wenke NIE ; Li ZHOU ; Siqi WANG ; Chao SONG ; Hang YU ; Wanwei LI ; Mengxiao LUAN ; Lu SUN ; Li YU
Journal of Environmental and Occupational Medicine 2026;43(3):270-277
Background Prenatal exposure to fine particulate matter (PM2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM2.5, compared with the PM2.5+siNC group, the PM2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM2.5-induced cortical damage in offspring mice during pregnancy.
2.Prognostic significance of TRIM28 elevation in non-M3 acute myeloid leukemia
Siqi GONG ; Cong LI ; Mengmeng FAN ; Huiping WANG ; Wanqiu ZHANG ; Xue LIANG ; Qianshan TAO ; Qiang HONG ; Zhimin ZHAI
Acta Universitatis Medicinalis Anhui 2026;61(2):301-308
ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia (AML) and its correlation with clinical indicators and prognosis, and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia (AML) patients. Clinical samples from non-M3 AML patients were collected, with TRIM28 expression levels measured using real-time quantitative PCR (qPCR). The analysis focused on correlations between TRIM28 expression and various clinical indicators, treatment efficacy, and patient prognosis. Furthermore, small interfering RNA (siRNA) technology was employed to downregulate TRIM28 expression in human primary AML cells (HL60 cell line). The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry, respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples (P<0.000 1), TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group (P<0.01), and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group, and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation, positively correlated with age, bone marrow blast, peripheral blood blast and white blood cell, negatively correlated with hemoglobin. In addition, interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis, and plays a key role in the proliferation and apoptosis of AML cells, suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.
3.Correlation of mitochondrial genetic differentiation and spatial variables of Oncomelania hupensis robertsoni in Yunnan Province
Yuanyuan ZHANG ; Jing SONG ; Yuwan HAO ; Zaogai YANG ; Xinping SHI ; Siqi NING ; Hongqiong WANG ; Chunhong DU ; Jihua ZHOU ; Zongya ZHANG ; Kai LI ; Shizhu LI ; Yi DONG
Chinese Journal of Schistosomiasis Control 2026;38(1):54-59
Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.
4.Integrated evidence chain (Eff-iEC) based effectiveness evaluation of a multifunctional traditional Chinese medicine formula: Taking Xiaoyao San as an example
Caiping HE ; Ye LUO ; Zhiqi LI ; Haocheng YANG ; Lu LIU ; Yingjie XU ; Xiaoyan CHEN ; Siqi HUANG ; Jincai WEN ; Xiaoyan ZHAN ; Zhaofang BAI ; Xu ZHAO ; Xiaohe XIAO
Science of Traditional Chinese Medicine 2026;4(1):96-103
The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate +" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.
5.Analysis of the global disease burden and trend of early-onset colorectal cancer
Zhanghan CHEN ; Siqi GAN ; Yiyuan CAO ; Linda LI ; Tianyu ZHANG ; Jia SONG ; Zhipeng QI ; Yunshi ZHONG
Chinese Journal of Clinical Medicine 2025;32(5):734-742
Objective To analyze the disease burden of early-onset colorectal cancer (EOCRC) at the global, regional, and national levels from 1990 to 2021, and to predict the disease burden trend from 2022 to 2026. Methods Based on the Global Burden of Disease (GBD) database, the incidence, mortality, and disability-adjusted life year (DALY) rate of EOCRC across 204 countries and regions from 1990 to 2021 were obtained. The time trends of these indicators were assessed by calculating the estimated annual percentage change (EAPC), and the contributions of ten risk factors to the EOCRC burden were analyzed. The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden from 2022 to 2026. Results From 1990 to 2021, the number of new global EOCRC cases increased from 107 310 to 211 890, with the incidence rising from 3.96 to 5.37 per 100 000 people. In 2021, global EOCRC incidence, mortality, and DALY rate increased with age; males had higher rates than females in terms of incidence, mortality, and DALY rate in all age groups. In 2021, East Asia had the highest number of new cases, deaths, and DALY. From 1990 to 2021, the global EAPC for incidence rate was 0.96%, and death rate was –0.38%. ARIMA model indicated that from 2022 to 2026, the global incidence of EOCRC would continue to rise, while mortality and DALY rate would be expected to decline. Conclusions The disease burden of EOCRC has significantly increased globally from 1990 to 2021, with notable regional, age, and sex differences. By 2026, the mortality and DALY rate of EOCRC will decline, while the incidence is expected to further increase, highlighting the urgency of taking active measures to address the growing trend of EOCRC.
6.Clinical efficacy of azithromycin for treatment of Mycoplasma pneumoniae pneumonia with gene mutations at site A2063G of 23S rRNA in children
Wen LI ; Tongyong LUO ; Fei WANG ; Bo ZHANG ; Yongxian JIANG ; Siqi HU
Journal of Chongqing Medical University 2025;50(11):1569-1572
Objective:To observe the clinical efficacy of azithromycin for the treatment of Mycoplasma pneumoniae pneumonia(MPP)with gene mutations at site A2063G of 23S rRNA in children.Methods:Data were retrospectively collected for 242 children diagnosed with MPP at Sichuan Provincial Maternity and Child Health Care Hospital from January to December 2023,in whom MPP was detected using targeted next-generation sequencing(tNGS).According to the presence or absence of mutations,the children were classified into mutation group(88 cases)and non-mutation group(154 cases).Results:Gene mutations at site A2063G of 23S rRNA were detected in 88 patients.The chest X-rays of both groups showed more lesions in the right lung than in the left lung.Both groups were treated with azithromycin and compared for differences in age,sex,duration of fever,C-reactive protein level,time to improvement of chest X-rays,days of medication,and response rate,with no significant differences found in the above indicators(P>0.05).However,the duration of respiratory symptoms was significantly longer in the mutation group than in the non-mutation group[(11.51±3.31)d vs.(10.06±3.63)d,P<0.05].Conclusion:Azithromycin is effective in treating MPP with gene mutations at site A2063G of 23S rRNA.
7.Emerging role of lysosomal regulation in Alzheimer's disease
Mengqi HAO ; Wenbo JI ; Yuankai GU ; Xinyu LU ; Li WANG ; Siqi LI ; Along HOU ; Chao GAO ; You YIN
Academic Journal of Naval Medical University 2025;46(4):518-523
Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.
8.Sishenwan Restores Intestinal Barrier in Rat Model of Diarrhea-predominant Irritable Bowel Syndrome Due to Spleen-kidney Yang Deficiency by Regulating Intestinal Flora and Short-chain Fatty Acids
Qian ZHANG ; Siqi LI ; HUYUNLIAN ; Na WEN ; Chaoqun HUANG ; Binbin LIU ; Chengxia SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):80-89
ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats, 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank, model, low-dose (3.51 g·kg-1) Sishenwan, high-dose (7.02 g·kg-1) Sishenwan, and Peifeikang (0.54 g·kg-1) groups, with 8 rats in each group. The blank group was fed conventionally, and the other groups were subjected to mother-child separation and Sennae Folium gavage (1 g·mL-1, 10 mL·kg-1) for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed, the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage, and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration, the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta (TGF-β), interleukin-10 (IL-10), and interleukin-22 (IL-22). Immumohistochemical staining (IHC) was performed to detect the positive expression of zonula occludens-1 (ZO-1) and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats, and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids (SCFAs) in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure, neat glands, and no inflammatory cell infiltration. In the model group, the colon tissue showcased a disorganized structure, irregular arrangement of glands, and inflammatory cell infiltration. Compared with the model group, the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure, regular arrangement of glands, and reduced inflammatory cell infiltration. Compared with the blank group, the modeling lowered the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.01), down-regulated the protein levels of ZO-1 and occludin in the colon tissue (P<0.01), and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents (P<0.05). Compared with the model group, low-dose and high-dose Sishenwan raised the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.05, P<0.01), and Peifeikang elevated the levels of TGF-β and IL-10 in the serum (P<0.01). High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin (P<0.05, P<0.01), increased the content of acetic acid and propionic acid in cecum contents (P<0.05), and decreased the content of butyric acid (P<0.05). The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group, Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae, Muribaculaceae, Akkermansiaceae, Ligilactobacillus, UBA3282, Akkermansia, and Corynebacterium while reducing the relative abundance of Oscillospiraceae, Desulfovibrionaceae, Lactobacillus, Romboutsia, and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation, increase the expression of tight junction proteins in the colonic mucosa, and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs, and the effect of high-dose Sishenwan is obvious.
9.Sishenwan Restores Intestinal Barrier in Rat Model of Diarrhea-predominant Irritable Bowel Syndrome Due to Spleen-kidney Yang Deficiency by Regulating Intestinal Flora and Short-chain Fatty Acids
Qian ZHANG ; Siqi LI ; HUYUNLIAN ; Na WEN ; Chaoqun HUANG ; Binbin LIU ; Chengxia SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):80-89
ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats, 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank, model, low-dose (3.51 g·kg-1) Sishenwan, high-dose (7.02 g·kg-1) Sishenwan, and Peifeikang (0.54 g·kg-1) groups, with 8 rats in each group. The blank group was fed conventionally, and the other groups were subjected to mother-child separation and Sennae Folium gavage (1 g·mL-1, 10 mL·kg-1) for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed, the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage, and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration, the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta (TGF-β), interleukin-10 (IL-10), and interleukin-22 (IL-22). Immumohistochemical staining (IHC) was performed to detect the positive expression of zonula occludens-1 (ZO-1) and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats, and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids (SCFAs) in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure, neat glands, and no inflammatory cell infiltration. In the model group, the colon tissue showcased a disorganized structure, irregular arrangement of glands, and inflammatory cell infiltration. Compared with the model group, the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure, regular arrangement of glands, and reduced inflammatory cell infiltration. Compared with the blank group, the modeling lowered the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.01), down-regulated the protein levels of ZO-1 and occludin in the colon tissue (P<0.01), and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents (P<0.05). Compared with the model group, low-dose and high-dose Sishenwan raised the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.05, P<0.01), and Peifeikang elevated the levels of TGF-β and IL-10 in the serum (P<0.01). High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin (P<0.05, P<0.01), increased the content of acetic acid and propionic acid in cecum contents (P<0.05), and decreased the content of butyric acid (P<0.05). The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group, Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae, Muribaculaceae, Akkermansiaceae, Ligilactobacillus, UBA3282, Akkermansia, and Corynebacterium while reducing the relative abundance of Oscillospiraceae, Desulfovibrionaceae, Lactobacillus, Romboutsia, and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation, increase the expression of tight junction proteins in the colonic mucosa, and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs, and the effect of high-dose Sishenwan is obvious.
10.Salidroside alleviates PM2.5-induced pulmonary fibrosis through PINK1/Parkin
Ruixi ZHOU ; Wenbo WU ; Limin ZHANG ; Meina WU ; Chen LIU ; Siqi LI ; Xiaohong LI ; Mengxiao LUAN ; Qin WANG ; Li YU ; Yumei LIU ; Wanwei LI
Journal of Environmental and Occupational Medicine 2025;42(10):1240-1246
Background Existing studies have confirmed that fine particulate matter (PM2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg−1 by gavage, n=10), PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 + saline by gavage, n=10), and Sal + PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 +Sal 60 mg·kg−1 by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

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