1.Factors affecting and identification of key environmental determinants of the Oncomelania hupensis snail density in the Yangtze River Delta based on machine learning models
Yinlong LI ; Qin LI ; Suying GUO ; Shizhen LI ; Lijuan ZHANG ; Chunli CAO ; Jing XU
Chinese Journal of Schistosomiasis Control 2026;38(1):14-19
Objective To identify factors affecting and key environmental factors of the Oncomelania hupensis snail density in the Yangtze River Delta region using machine learning methods. Methods Administrative village-level O. hupensis snail survey data in the Yangtze River Delta (including Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province) from 2011 to 2021 were retrieved from the Information Management System for Parasitic Disease Control of Chinese Center for Disease Control and Prevention. Environmental factor data were captured from the Google Earth Engine platform, including elevation, slope, terrain, normalized difference vegetation index (NDVI), vegetation type, soil type, total petroleum hydrocarbon (TPH), ammonium nitrogen, inorganic nitrogen, dissolved oxygen, pH of water, chemical oxygen demand (COD) and inorganic phosphorus, and climatic factor data in the study region were retrieved from the Copernicus Climate Data Store, including annual precipitation, aridity index and annual mean temperature (AMT). O. hupensis snail survey data in the Yangtze River Delta region from 2011 to 2021 were randomly divided into a training set (70%) and a test set (30%), and five machine learning models were selected for machine learning model construction and comparative analysis of the O. hupensis snail density using the software R 4.3.0, including random forest (RF), eXtreme gradient boosting (XGBoost), support vector machine (SVM), gradient boosting machine (GBM) and neural network (NN). The XGBoost model was employed to construct a predictive model for the O. hupensis snail density, and the impact of each environmental factor on O. hupensis snail distribution was quantified. The SHapley Additive exPlanations (SHAPs) values were calculated to estimate the average contribution of each variable to the model prediction, and the core environmental factors affecting the O. hupensis snail population density were screened. Results Among the five machine learning models, the XGBoost model exhibited the optimal comprehensive performance, with the coefficient of determination (R2) of 0.855, mean squared error (MSE) of 0.188, root mean squared error (RMSE) of 0.434 and mean absolute error (MAE) of 0.155, respectively. Analysis of factors affecting the O. hupensis snail density with the XGBoost model showed that among the 16 environmental factors, the top four high-impact factors ranked by SHAPs values included annual precipitation, elevation, aridity index and NDVI, with cumulative SHAPs contributions of 75%, which was higher than that of other environmental factors. If NDVI was higher than 0.6, the O. hupensis snail density increased with NDVI and peaked if NDVI was 0.8 (1.60 snails/0.1 m2). The O. hupensis snail density increased with elevation if the elevation ranged from 14 to 40 m, and slowly rose if the annual precipitation ranged from 900 to 1 300 mm, and then increased rapidly to the peak (1.52 snails/0.1 m2) if the annual precipitation ranged from 1 300 to 1 500 mm. In addition, the O. hupensis snail density increased rapidly to the maximum (1.60 snails/0.1 m2) if the aridity index ranged from 0.8 to 1.1, and decreased gradually if the aridity index exceeded 1.1. Conclusions The XGBoost model shows excellent performance in prediction of the O. hupensis snail density and identification of key environmental factors in the Yangtze River Delta region. Annual precipitation, elevation, aridity index and NDVI are key environmental factors affecting the distribution and density of O. hupensis snails in the Yangtze River Delta region.
2.Research progress on association and mechanisms of copper dyshomeostasis with development of chronic diseases
Haibo ZHANG ; Jinsong FAN ; Xuezhen LIU ; Pinpin LONG
Journal of Environmental and Occupational Medicine 2026;43(4):516-526
Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.
3.Progress of schistosomiasis control in the People’s Republic of China in 2024
Junyi HE ; Lijuan ZHANG ; Fan YANG ; Hui DANG ; Yinlong LI ; Suying GUO ; Shizhen LI ; Chunli CAO ; Jing XU ; Shizhu LI
Chinese Journal of Schistosomiasis Control 2025;37(3):223-231
To understand the progress of, summarize the lessons learned from and analyze the challenges in the national schistosomiasis elimination program of China in 2024, this article presented the endemic situation of schistosomiasis and national schistosomiasis surveillance results in the People’s Republic of China in 2024. By the end of 2024, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate schistosomiasis elimination achievements, and 7 provinces of Jiangsu, Sichuan, Yunnan, Hubei, Hunan, Anhui and Jiangxi maintained the criteria of schistosomiasis transmission interruption. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2024, including 26 061 endemic villages covering 73 630 500 residents at risk of infections. Among the 450 counties (cities, districts) endemic for schistosomiasis, 388 (86.22%) achieved the criteria of schistosomiasis elimination and 62 (13.78%) achieved the criteria of transmission interruption. In 2024, a total of 4 102 624 individuals received immunological tests for schistosomiasis in China, with 44 823 sero-positives identified (1.09% seroprevalence), and a total of 169 722 individuals received parasitological examinations, with 1 egg-positives detected. A total of 27 321 cases with advanced schistosomiasis were documented in China by the end of 2024. In 2024, a total of 575 686 bovines were raised in schistosomiasis-endemic villages of China, and 113 842 bovines received immunological tests, with 235 sero-positives detected (0.21% seroprevalence), while no egg-positives were identified among the 167 475 bovines receiving parasitological examinations. In 2024, snail survey was performed covering an area of 680 498.27 hm2 in China, and 190 778.66 hm2 snail habitats were identified, including 59.09 hm2 emerging snail habitats and 704.23 hm2 reemerging snail habitats. In 2024, a total of 19 665 schistosomiasis patients receiving chemotherapy with praziquantel in China, and expanded chemotherapy was given to humans at 571 722 person-times and to bovines at 306 740 herd-times. In addition, snail control with chemical treatment covered 117 111.37 hm2 snail habitats across China in 2024, and the actual area of chemical treatment was 66 562.95 hm2, while environmental improvements were performed in snail habitats covering an area of 1 374.26 hm2. The national schistosomiasis surveillance results showed that the mean prevalence rates of Schistosoma japonicum infections were both 0 among humans and bovines in China in 2024, and no S. japonicum infection was detected in snails. These data demonstrated that the prevalence of schistosomiasis remained at a low level in China in 2024; however, the areas of snail habitats remained high and the number of fenced cattle showed a slight increase. To address these risks, it is imperative to maintain the integrated strategy with an emphasis on management of the source of S. japonicum infection and intensified snail control in high-risk areas, and to reinforce schistosomiasis surveillance and forecast and snail control in high-risk areas.
4.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.
5.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.
6.Mechanism of the pretreatment with electroacupuncture of "biaoben acupoint combination" for regulating cardiomyocyte mitochondrial fission in the rats of myocardial ischemia-reperfusion injury.
Yanlin ZHANG ; Song WU ; Qianru GUO ; Yuntao YU ; Sunyi WANG ; Yuqi WEI ; Xiaoman WAN ; Zhen LU ; Xiaoru HE
Chinese Acupuncture & Moxibustion 2025;45(3):335-344
OBJECTIVE:
To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism.
METHODS:
Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected.
RESULTS:
Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group.
CONCLUSION
Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals
;
Electroacupuncture
;
Male
;
Rats, Sprague-Dawley
;
Myocardial Reperfusion Injury/physiopathology*
;
Myocytes, Cardiac/cytology*
;
Rats
;
Acupuncture Points
;
Mitochondrial Dynamics
;
Humans
;
Reactive Oxygen Species/metabolism*
;
NF-E2-Related Factor 2/genetics*
;
Superoxide Dismutase/metabolism*
7.Moxibustion for central obesity with phlegm-dampness constitution: a randomized controlled trial.
Yanji ZHANG ; Dan WEI ; Wei HUANG ; Jiajie WANG ; Xia CHEN ; Chengwei FU ; Benlu YU ; Yingrong ZHANG ; Zhongyu ZHOU
Chinese Acupuncture & Moxibustion 2025;45(8):1053-1060
OBJECTIVE:
To observe the efficacy and safety of moxibustion in treating patients with central obesity of phlegm-dampness constitution.
METHODS:
A total of 66 patients with central obesity of phlegm-dampness constitution were randomly assigned to a moxibustion group (n=33, 3 cases dropped out) and a sham moxibustion group (n=33, 4 cases dropped out). The moxibustion group received mild moxibustion combined with lifestyle intervention; the moxibustion was applied at Shenque (CV8) and bilateral Zusanli (ST36), 30 min per session, maintaining a local skin temperature of (43±1) ℃. The sham moxibustion group received simulated moxibustion combined with lifestyle intervention; the simulated moxibustion was applied at the same acupoints, with the same session length, but with a maintained skin temperature of (37±1) ℃. Both groups were treated once every other day, three times per week for 8 consecutive weeks. Obesity-related physical indicators (waist circumference, hip circumference, body weight, body fat percentage, body mass index [BMI]), constitution evaluation indicators (phlegm-dampness constitution conversion score, symptom score), the impact of weight on quality of life-lite (IWQOL-Lite), the hospital anxiety and depression scale (HADS), and the incidence of adverse events were measured before and after treatment, and after 4 weeks of follow-up.
RESULTS:
Compared with before treatment, both groups showed significant reductions in waist circumference, hip circumference, body weight, body fat percentage, BMI, phlegm-dampness constitution conversion score and symptom score, IWQOL-Lite, and both anxiety and depression subscale scores of HADS after treatment and at follow-up (P<0.001). These improvements were significantly greater in the moxibustion group than those in the sham moxibustion group (P<0.001, P<0.01, P<0.05). One patient in the moxibustion group experienced a mild burn that resolved with routine care; the incidence of adverse reactions was 3.0% (1/33) in the moxibustion group and 0% (0/33) in the sham moxibustion group, with no statistically significant difference (P>0.05).
CONCLUSION
On the basis of lifestyle intervention, moxibustion effectively improves obesity-related physical indicators, enhances quality of life, alleviates anxiety and depression, and improves the phlegm-dampness constitution in patients with central obesity. These benefits persist for at least 4 weeks after treatment.
Humans
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Moxibustion
;
Male
;
Female
;
Middle Aged
;
Adult
;
Obesity, Abdominal/psychology*
;
Acupuncture Points
;
Treatment Outcome
;
Aged
;
Quality of Life
;
Young Adult
;
Body Mass Index
8.Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer.
Shizhen GENG ; Tingting XIANG ; Yaru SHI ; Mengnian CAO ; Danyu WANG ; Jing WANG ; Xinling LI ; Haiwei SONG ; Zhenzhong ZHANG ; Jinjin SHI ; Junjie LIU ; Airong LI ; Ke SUN
Acta Pharmaceutica Sinica B 2025;15(2):1084-1097
Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.
9.Hyssopus cuspidatus extract inhibited OVA-sensitized allergic asthma through PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.
Yali ZHANG ; Huiming PENG ; Jingjing LI ; Pan LV ; Mengru ZHANG ; Xu WANG ; Siyu WANG ; Siying ZHU ; Jiankang LU ; Xuepeng FAN ; Jinbo FANG
Chinese Herbal Medicines 2025;17(3):539-547
OBJECTIVE:
To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma.
METHODS:
Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation.
RESULTS:
Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine.
CONCLUSION
HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.
10.Structurally diverse sesquiterpenoids with anti-MDR cancer activity from Penicillium roqueforti.
Shuyuan MO ; Nanjin DING ; Zhihong HUANG ; Jun YAO ; Weiguang SUN ; Jianping WANG ; Yonghui ZHANG ; Zhengxi HU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):504-512
Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC50) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L-1, which was 65-fold more potent than PTX alone (IC50 3.26 μmol·L-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry*
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Humans
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Sesquiterpenes/isolation & purification*
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Cell Line, Tumor
;
Molecular Structure
;
Drug Resistance, Neoplasm/drug effects*
;
Antineoplastic Agents/pharmacology*
;
Drug Resistance, Multiple/drug effects*
;
Molecular Docking Simulation

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