1.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
2.Comprehensive Analysis of Oncogenic, Prognostic, and Immunological Roles of FANCD2 in Hepatocellular Carcinoma: A Potential Predictor for Survival and Immunotherapy.
Meng Jiao XU ; Wen DENG ; Ting Ting JIANG ; Shi Yu WANG ; Ru Yu LIU ; Min CHANG ; Shu Ling WU ; Ge SHEN ; Xiao Xue CHEN ; Yuan Jiao GAO ; Hongxiao HAO ; Lei Ping HU ; Lu ZHANG ; Yao LU ; Wei YI ; Yao XIE ; Ming Hui LI
Biomedical and Environmental Sciences 2025;38(3):313-327
OBJECTIVE:
Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.
METHODS:
Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.
RESULTS:
FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.
CONCLUSION
To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans
;
Carcinoma, Hepatocellular/diagnosis*
;
Liver Neoplasms/diagnosis*
;
Immunotherapy
;
Fanconi Anemia Complementation Group D2 Protein/metabolism*
;
Prognosis
;
Male
;
Female
;
Middle Aged
;
Biomarkers, Tumor/metabolism*
3.Independent and Interactive Effects of Air Pollutants, Meteorological Factors, and Green Space on Tuberculosis Incidence in Shanghai.
Qi YE ; Jing CHEN ; Ya Ting JI ; Xiao Yu LU ; Jia le DENG ; Nan LI ; Wei WEI ; Ren Jie HOU ; Zhi Yuan LI ; Jian Bang XIANG ; Xu GAO ; Xin SHEN ; Chong Guang YANG
Biomedical and Environmental Sciences 2025;38(7):792-809
OBJECTIVE:
To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases.
METHODS:
TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.
RESULTS:
Increased TB risk was linked to PM 2.5, PM 10, and rainfall, whereas NO 2, SO 2, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM 2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM 10 ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO 2 ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO 2 ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM 2.5 on TB.
CONCLUSION
Exposure to PM 2.5, PM 10, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology*
;
Humans
;
Air Pollutants/analysis*
;
Tuberculosis/epidemiology*
;
Incidence
;
Meteorological Concepts
;
Particulate Matter/adverse effects*
;
Environmental Exposure
;
Male
;
Female
;
Adult
;
Air Pollution
;
Middle Aged
4.Scientific analysis and usage reassessment of suspected medicinal cinnabar unearthed from Mawangdui Tomb No.3 of the Han Dynasty.
Ning-Ning XU ; Ting-Yan REN ; Ming-Jie LI ; Pan XIAO ; Guo-Hui SHEN ; Ji-Qing BAI ; Qi LIU
China Journal of Chinese Materia Medica 2025;50(11):2915-2923
Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient
;
China
;
Humans
;
Medicine, Chinese Traditional/history*
;
Archaeology
;
Drugs, Chinese Herbal/history*
;
Spectroscopy, Fourier Transform Infrared
;
Spectrum Analysis, Raman
;
Mercury Compounds
5.Total triterpenoids from Hovenia dulcis increase sensitivity of A549/DDP to cisplatin by inducing Nrf2-mediated ferroptosis
Xiao-lan KUANG ; Dong-ning SHEN ; Ting FU ; Fan WU ; Jian-zhan YANG ; Jin-lang ZHONG ; Bo LIU ; Fang-fang XU
Chinese Pharmacological Bulletin 2025;41(11):2128-2134
Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.
6.Study on Colorimetric Sensor Array Based on Enzymatic Method for Highly Selective Detection of Sarin
Lian-Bo JIANG ; Guo-Hong LIU ; Zhuang-Hu XU ; Jian LI ; Yong-Ling SHEN ; Cai-Xia XU ; Chuan-Qin ZANG ; Yan-Hua XIAO ; Dan-Ping LI ; Ting LIANG
Chinese Journal of Analytical Chemistry 2025;53(5):832-841,中插21-中插23
Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.
7.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):189-207
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
8.Design of new type of elastic gloves for burn scar rehabilitation
Ting SHEN ; Hai-yang ZHAO ; Xiao-chun JIAO ; Bao-li CHEN ; Zhi-juan WANG ; Li-na WANG ; Xiang-yang ZHAO ; Qin ZHOU
Chinese Medical Equipment Journal 2025;46(8):118-120
Objective To design a new type of elastic gloves for burn scar rehabilitation to solve the problems of conventional elastic gloves in pressure distribution,elasticity maintenance and absorption of sweat stains.Methods The new elastic gloves was made of non-woven fabric by spandex material,which was composed of external and internal parts.The main body of the external part was used as the primary structure of the gloves,which was provided with a sealing strip,a storage bag,a drawstring,etc.The internal part consisted of a bonding sheet,an elastic band,a fiber sheet,an absorbent sponge,some breathable holes,etc.Results The new elastic gloves designed could be used for the pressure therapy for the scars on the opisthenar,palm side,finger web and purlicue with scar proliferation inhibitted effectively,and the breathable hole and absorbent sponge contributed to the absorption of the sweat of the patient.Conclusion The new type of elastic gloves gains advantages in elasticity,wearing comfort and effectiveness of the pressure therapy for purlicue and finger web,and can be used for the pressure therapy to inhibit proliferative scarring after burns.[Chinese Medical Equipment Journal,2025,46(8):118-120]
9.Experimental study on alternative method of local lymph node assay using bromodeoxyuridine with flow cytometry(LLNA:BrdU-FCM)for skin sensitization evaluation of cosmetics
Xiao-jun LYU ; Ju ZHANG ; Sen WU ; Xiao-ling XU ; Meng-ting SHI ; Jin-jing XU ; Wang-ping PAN ; Jia-te SHEN ; Kai-yong HE
Chinese Pharmacological Bulletin 2025;41(4):793-799
Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25%hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25%HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90%,specificity of 100%,positive prediction rate of 100%,negative prediction rate of 83%,false positive rate of 0%,false negative rate of 17%and accuracy of 93%.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.
10.Total triterpenoids from Hovenia dulcis increase sensitivity of A549/DDP to cisplatin by inducing Nrf2-mediated ferroptosis
Xiao-lan KUANG ; Dong-ning SHEN ; Ting FU ; Fan WU ; Jian-zhan YANG ; Jin-lang ZHONG ; Bo LIU ; Fang-fang XU
Chinese Pharmacological Bulletin 2025;41(11):2128-2134
Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

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