1.Effect of Simiaowan on Promoting Ileal Uric Acid Excretion by Modulating Gut Microbiota to Improve Intestinal Barrier Function and Upregulate ABCG2 Expression in Rats
Yuan ZHANG ; Zhongyou ZHANG ; Huilin FENG ; Lian DUAN ; Lingchun WANG ; Hao DAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):101-112
ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate (ATP) binding cassette transporter G2 (ABCG2) expression in hyperuricemic (HUA) rats, and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley (SD) rats were randomized into a normal group, a model group, low-dose (282.6 mg·kg-1) and high-dose (565.2 mg·kg-1) Simiaowan groups, and a Benzbromarone (4.7 mg·kg-1) group. The HUA model was established via intraperitoneal injection of potassium oxonate (ip) combined with oral gavage of hypoxanthine (ig) for 14 days. Following modeling, treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining, and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay (ELISA) quantified tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), lipopolysaccharide (LPS), diamine oxidase (DAO), and D-lactic acid (D-LA) levels. Real-time polymerase chain reaction (Real-time PCR), Western blot, and immunohistochemistry assessed the expression of Claudin-1, Occludin, occludens-1 (ZO-1), and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group, the model group exhibited epithelial shedding in the ileal villus, structural disruption, infiltration of extensive inflammatory cells, and significantly elevated Chiu's scores (P<0.01). The DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum were markedly increased (P<0.01), while mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion, were significantly reduced (P<0.01). Compared with the model group, the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus, significantly lowered Chiu's scores (P<0.01), significantly reduced DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum (P<0.01), and upregulated mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion (P<0.01). The 16S rDNA results showed that in the model group, the α-diversity index of the ileal microbiota was increased, and species diversity and richness were enhanced, with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased, and the abundance of pathogenic bacteria was increased, with butyrate-producing bacteria showing a low abundance. In contrast, Simiaowan at all doses reduced species diversity and richness, regulated microbiota dysfunction, and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria, decreased the abundance of harmful bacteria, and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.
2.Analysis of regulation of prognosis,immune infiltration,and ferroptosis in sarcoma based on stemness index model
Jingxian WEI ; Lian MENG ; Hao SUN ; Tiantian ZHANG ; Chunxia LIU
Chinese Journal of Tissue Engineering Research 2025;29(19):4151-4160
BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.
3.Current research status and application prospects of mesenchymal stem cell-derived exosomes in islet transplantation
Rui LI ; Dianxiang WANG ; Zhaowei LIANG ; Bing HAN ; Hao LIAN
Organ Transplantation 2025;16(1):163-168
Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.
4.ATG5 counteracts nutritional stress in human hepatoblastoma HepG2 cells by regulating autophagic flux
Lian ZHAO ; Dongyun XIANG ; Huiyi WU ; Hao SUN ; Jinghuan DENG
Journal of Army Medical University 2025;47(13):1454-1462
Objective To investigate the effect of nutritional deficiency on autophagic flux in human hepatoblastoma HepG2 cells and the autophagy-dependent molecular pathway mediated by ATG5 against nutritional stress.Methods Lentiviral siRNA knockdown of ATG5 was performed to knock down the expression in HepG2 cells,and the transfection was verified by Western blotting and qRT-PCR.HBSS was used to treat HepG2 cells for 0,1,2,3,4,5,6 and 7 h for starvation-induced autophagy.Monodansylcadaverine(MDC)fluorescence staining was employed to detect the formation of intracellular autophagic vesicles.Western blotting was performed to measure the expression changes in microtubule-associated protein 1A/1B-light chain 3(LC3),autophagy receptor protein(sequestosome 1,P62),autophagy-related gene 5(ATG5)and nutrient stress pathway(AMPK/mTOR pathway)related proteins.CCK-8 assay was utilized to test cell proliferation.Results Compared with the HepG2 cells under conventional culture medium,starvation induction resulted in more autophagic vacuoles(accumulation of autofluorescent marker,MDC),which peaked at 6 h of starvation(P<0.000 1),up-regulated protein levels of LC3B-Ⅱ and ATG5(P<0.05),decreased protein expression of P62(P<0.05),gradual activation of the AMPK/mTOR pathway with elapse of starvation time,and increase in the intensity of autophagic flux.However,in the HepG2 cells with ATG5 knockdown,starvation treatment led to decreased ATG5 expression,no significant difference in LC3B-II and P62 changes,inhibited autophagic flux,and suppressed cell proliferation(P<0.000 1).Conclusion Human hepatoblastoma HepG2 cells can regulate autophagic flux to against nutritional stress by inducing ATG5 expression.
5.Clinical application of physician-modified stent grafts in complex aortic disease
Hao WANG ; Bin LIU ; Zhiwen ZHANG ; Zhe ZHANG ; Zhao LIU ; Mingyuan LIU ; Wenrui LI ; Lishan LIAN ; Bodong XU ; Hai FENG
International Journal of Surgery 2025;52(7):439-443
In the past, aortic dissection, aortic aneurysm, and other aortic diseases, primarily rely on surgical intervention. In recent years, due to breakthroughs in materials science, endovascular therapy has become the first choice for the surgical treatment of most aortic diseases. However, traditional endovascular repair cannot fully meet the clinical needs for certain complex lesions involving the aortic arch and the originations of visceral arteries. The emergence of physician-modified stent technology has brought new hope for the treatment of complex aortic diseases. This article provides a detailed introduction to the concept, development, technical characteristics, and applications of physician-modified stents in the treatment of aortic diseases, analyzing their advantages and limitations. Physician-modified stents serve as a powerful complement to traditional endovascular interventions and commercial branched stents, yet further research and refinement are still required.
6.Research progress on pharmacological effects and mechanism of α-asarone and β-asarone in Acori Tatarinowii Rhizoma.
Hao WANG ; Lei GAO ; Jin-Lian ZHANG ; Ling-Yun ZHONG ; Shu-Han JIN ; Xiao-Yan CHEN ; Wen ZHANG ; Jia-Wen WEN
China Journal of Chinese Materia Medica 2025;50(9):2305-2316
Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives
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Acorus/chemistry*
;
Anisoles/chemistry*
;
Rhizome/chemistry*
;
Drugs, Chinese Herbal/chemistry*
;
Humans
;
Animals
7.Domestication progress of endangered Chinese medicinal material Fritillariae Cirrhosae Bulbus.
Ting XIAO ; Ming-Hao YANG ; Qiu-Ling WANG ; Qiang LYU ; Yu-Qing ZHENG ; Lian-Cheng XU ; Ma YU ; Jian-He WEI
China Journal of Chinese Materia Medica 2025;50(16):4483-4489
Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry*
;
Endangered Species
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Plants, Medicinal/growth & development*
;
Drugs, Chinese Herbal/economics*
;
China
9.Research progress of an immune checkpoint molecule VISTA in hematological tumors
Zi-Jun TANG ; Han-Xue ZHENG ; Hao XIONG ; Lian-Sheng ZHANG ; Li-Juan LI
Medical Journal of Chinese People's Liberation Army 2025;50(6):672-678
Research on immune checkpoints such as programmed death protein-1(PD-1)and cytotoxic T lymphocyte antigen-4(CTLA-4)has provided new directions for tumor treatment.V-domain immunoglobulin suppressor of T-cell activation(VISTA)is an emerging immune checkpoint within the B7 family.Functioning as both a ligand and a receptor,VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells,myeloid cells and T lymphocytes.It plays a crucial role in regulating autoimmunity,inflammatory response and tumor immunity.The non-redundant interactions between VISTA and other immune checkpoints,such as PD-1,may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance.This review summarizes the recent research progress on VISTA in hematological tumors,aiming to provide new insights into its application in the treatment of these malignancies.
10.Protective effects and mechanisms of sodium pyruvate on storage lesions in human red blood cells
Haoning CHEN ; Qi MIAO ; Qiang GAO ; Xin SUN ; Shunyu MEI ; Li WANG ; Yun LIAN ; Honglin LUO ; Chenjie ZHOU ; Hao LI
Chinese Journal of Blood Transfusion 2025;38(6):833-838
Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H
O
), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H
O
. After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na
/K
-ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na
/K
-ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

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