1.Celastrol-loaded ginsenoside Rg3 liposomes boost immunotherapy by remodeling obesity-related immunosuppressive tumor microenvironment in melanoma.
Hongyan ZHANG ; Jingyi HUANG ; Yujie LI ; Wanyu JIN ; Jiale WEI ; Ninghui MA ; Limei SHEN ; Mancang GU ; Chaofeng MU ; Donghang XU ; Yang XIONG
Acta Pharmaceutica Sinica B 2025;15(5):2687-2702
Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8+ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8+ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.
2.The crucial function of IDO1 in pulmonary fibrosis: From the perspective of mitochondrial fusion in lung fibroblasts and targeted molecular inhibition.
Lei WANG ; Shanchun GE ; Ye ZHANG ; Deqin FENG ; Ting ZHU ; Louqian ZHANG ; Chaofeng ZHANG
Acta Pharmaceutica Sinica B 2025;15(6):3125-3148
The pathogenesis of pulmonary fibrosis (PF) is complex. It is characterized by myofibroblast hyperplasia and deposition of collagen protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in lung fibroblasts and epithelial cells, but its functions in lung homeostasis and diseases remain elusive. Here, we characterize the critical role of IDO1 in PF patients and bleomycin (BLM)-induced PF mouse models. We find that IDO1 is significantly upregulated in the fibrotic lungs of patients and mice, showing a positive correlation with genes characteristic of fibrosis. Functionally, IDO1 knockout inhibits lung fibroblast proliferation, differentiation, mitochondrial biogenesis, and mitochondrial oxidative phosphorylation. Conversely, IDO1 overexpression and accumulation of kynurenine (Kyn) exacerbate progressive lung fibrosis. Mechanistically, IDO1-deletion activated profound mitochondrial fusion-enhanced potentially the capacity for fatty acid oxidation, along with activation of de novo glycolytic serine/glycine synthesis pathways and mitochondrial one-carbon metabolism. Wedelolactone (WEL), a small molecule IKK inhibitor, is found to strongly bind to IDO1 and effectively protect mice from PF in an IDO1-dependent manner. Collectively, this study characterizes a promotor role for IDO1 in PF and suggests a potential avenue of targeting IDO1 to treat lung diseases.
3.Research progress on new techniques and methods for identifying active ingredients in traditional Chinese medicine.
Jiaxin ZHANG ; Xinhao ZHU ; Chaofeng ZHANG ; Wangning ZHANG ; Jiangwei TIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1153-1170
Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine (TCM), substantially advancing research and development efforts. Spectrum-effect correlation analysis, affinity ultrafiltration, high-content screening (HCS) imaging, and cell membrane chromatography (CMC) have emerged as essential tools, effectively linking TCM chemical constituents to their biological effects, thereby enabling efficient active ingredient screening. Additionally, molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms, enhancing understanding of its therapeutic potential. Computer-aided techniques facilitate TCM active ingredient identification, optimizing the screening process for efficiency and cost-effectiveness. Molecular probe technology, as an emerging methodology, enables precise and rapid screening for novel therapeutic drug discovery. Ongoing technological advancement in this field indicates promising future developments, potentially leading to more effective and targeted TCM-based therapies.
Drugs, Chinese Herbal/chemistry*
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Medicine, Chinese Traditional/methods*
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Humans
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Drug Discovery/methods*
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Animals
4.Research on microscopic histochemical localization of Astragalus membranaceus and its application
Yong HUANG ; Shengchao SHI ; Jian ZHANG ; Chaofeng ZHANG
Journal of China Pharmaceutical University 2025;56(5):566-571
This study compared the chemical composition differences among various root tissues of Astragalus membranaceus through optimization of histochemical localization methods, thereby providing some reference for targeted extraction and enrichment of bioactive components. The chloral hydrate permeabilization technique was enhanced with sodium nitrite-aluminum nitrate-sodium hydroxide reagent for flavonoid staining. Comparative analyses of total saponins, total flavonoids, and astragaloside IV content in xylem, phloem, and periderm tissues were performed using ultraviolet-visible spectroscopy (UV-Vis) and high-performance liquid chromatography (HPLC). By optimizing staining protocols, interference from natural pigmentation was successfully eliminated, thereby enhancing the visualization of tissue-specific chemical distribution. Quantitative analysis revealed that the phloem contained the highest total saponins (6.92%), while the periderm exhibited peak total flavonoids (0.876%) and exclusive enrichment of astragaloside IV (0.850%). The refined histochemical localization method enables precise characterization of phytochemical distribution across root tissues, which can offer guidance for selective extraction and enrichment strategies, and comprehensively promote the utilization and development of Astragalus membranaceus resources.
5.Research Progress on Dendrobii Officinalis Caulis as Medicinal and Edible Traditional Chinese Medicine
Yang HU ; Mian ZHAO ; Yuxuan QIU ; Debao YE ; Yangqing LIU ; Chaofeng ZHANG ; Haibo WANG ; Jian-Ming CHENG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(1):94-108
Tiepishihu(Dendrobii officinalis Caulis)is a medicinal and food source herbal medicine with the effect of benefiting stomach and promoting fluid,nourishing Yin and clearing heat.It has rich chemical components and pharmacological activities,with anti-inflammatory,anti-bacterial,anti-oxidation,anti-tumor,immunomodulatory,blood press regulation,hypoglycemic effects.It is not only used as medicinal food and health care products,but also widely used in medicine,such as Shihu Yeguang Wan,Compound fresh dendrobium granules and other drugs,with high medicinal and economic value.This paper summarized the resource distribution,chemical composition,pharmacological activities,and medicine and food of Dendrobii officinalis Caulis,and analyzed its application status,laying a theoretical foundation for the sustainable development,medicinal and food homologous development and comprehensive utilization of Dendrobii officinalis Caulis.
6.Prediction of the clinical supply of blood components in Xi′an City from 2023 to 2025
Linghao ZHANG ; Jin WANG ; Bei YAO ; Xiaoyue CHU ; Zhendong SUN ; Chaofeng MA
Chinese Journal of Preventive Medicine 2024;58(8):1213-1218
Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x(1)( t+1)=1.16e 0.04t, x(1)( t+1)=1.04e 0.12t and x(1)( t+1)=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.
7.Prediction of the clinical supply of blood components in Xi′an City from 2023 to 2025
Linghao ZHANG ; Jin WANG ; Bei YAO ; Xiaoyue CHU ; Zhendong SUN ; Chaofeng MA
Chinese Journal of Preventive Medicine 2024;58(8):1213-1218
Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x(1)( t+1)=1.16e 0.04t, x(1)( t+1)=1.04e 0.12t and x(1)( t+1)=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.
8.Short term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costoosteochondral autograft
Chaofeng XING ; Zhiyu HU ; Xiazhi LIU ; Tao YANG ; Jia CHEN ; Zirun XIAO ; Li SONG ; Beibei CHENG ; Yingjie XIONG ; Guangchao ZHANG ; Yongsheng HE ; Gaowei ZHANG
Chinese Journal of Microsurgery 2024;47(3):280-286
Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.
9.Esophageal squamous cell carcinoma exosomal miR-181b-5p promotes tumor associated macrophage polarization by inhibiting PTEN
Hui FAN ; Naikuo ZHAO ; Linlin CHEN ; Zhiguo LI ; Miao LIU ; Yuanying ZHANG ; Chaofeng ZHOU
Chinese Journal of Immunology 2024;40(7):1441-1446
Objective:To investigate the effect and mechanism of esophageal squamous cell carcinoma exosomal miR-181b-5p to the polarization of M2 macrophages.Methods:Extracted and identified exosomes from esophageal squamous cell carcinoma,and detected the expression of miR-181b-5p in esophageal squamous cell carcinoma cells and their exosomes by qRT-PCR.M0 type macro-phages were divided into PBS group,HEEC exo group,Eca-109 exo group,miR-NC exo group,miR-181b-5p exo group,miR-NC group,miR-181b-5p mimic group,si-NC group,si-PTEN group,miR-181b-5p exo+PTEN group.qRT-PCR was used to detect the expressions of CD163,CD206,iNOS and TNF-α in each group.The targeting relationship between miR-181b-5p and PTEN were veri-fied by double luciferase reporter gene experiment.Results:miR-181b-5p was significantly overexpressed in esophageal squamous cell carcinoma cells TE-13,TE-12,TE-10,Eca-109,KYSE30 and their exosomes(P<0.001).Compared with miR-NC group,the expression of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p mimic group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).The results of double luciferase reporter genes showed that PTEN was the target gene of miR-181b-5p.Compared with si-NC group,the expressions of CD163 and CD206 in cells were significantly upregu-lated in the si-PTEN group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with PBS group,the expressions of CD163 and CD206 in cells were significantly upregulated in the Eca-109 exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-NC exo group,the expressions of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-181b-5p exo group,the expressions of CD163 and CD206 in cells were significantly downregulated in the miR-181b-5p exo+PTEN group,as well as the expressions of iNOS and TNF-α were significantly upregulated(P<0.001).Conclusion:Exosomal miR-181b-5p inhibits PTEN expressions to promote M2 macrophage polarization.
10.Clinical effect of trapezoidal transparent corneal incision during phacoemulsi-fication
Chaofeng YUAN ; Fei CHEN ; Wenna GAO ; Chengxia MA ; Xiaohua ZHAO ; Ling ZHANG ; Fengyan ZHANG
Recent Advances in Ophthalmology 2024;44(8):619-622
Objective To explore the clinical effect of a trapezoidal transparent corneal incision during phacoemulsi-fication.Methods A total of 57 patients(68 eyes)undergoing phacoemulsification were selected and divided into a con-ventional incision group and a trapezoidal incision group using a random number table method.There were 28 patients(34 eyes)in the conventional incision group,including 15 eyes(males)and 19 eyes(females),with an age range of 41-82(65.0±10.1)years;and there were 29 patients(34 eyes)in the trapezoidal incision group,including 21 eyes(males)and 13 eyes(females),with an age range of 46-87(66.0±11.1)years.All patients underwent cataract phacoemulsification combined with intraocular lens(IOL)implantation.A 3.0 mm transparent corneal incision was made for patients in the conventional incision group,while an improved trapezoidal transparent corneal incision was made for patients in the trape-zoidal incision group.The uncorrected visual acuity,intraocular pressure,corneal astigmatism,and incidence of intraoper-ative and postoperative complications were compared between the two groups.Results The uncorrected visual acuity of patients in the trapezoidal incision group was better than that of patients in the conventional incision group at 1 week and 3 months after surgery,and the differences were statistically significant(both P<0.05).There was no statistically significant difference in intraocular pressure and corneal astigmatism between the two groups of patients at 1 week,1 month,and 3 months after surgery(all P>0.05).The number of eyes with anterior chamber collapse and the number of eyes requiring a watertight incision in the conventional incision group were greater than those in the trapezoidal incision group during sur-gery,and the differences were statistically significant(both P<0.05).The number of eyes with incision edema and the number of eyes with incision gap in the conventional incision group were greater than those in the trapezoidal incision group after surgery,and the differences were statistically significant(both P<0.05).In the conventional incision group,IOL was displaced in 18 eyes due to the shallow anterior chamber and then returned to normal after the formation of the anterior chamber through a watertight incision during surgery;during the formation,iris prolapse and incarceration occurred in 2 eyes,and IOL rotation or incarceration occurred in 3 eyes.In the trapezoidal incision group,3 eyes had a shallow anterior chamber after surgery,and a watertight incision was used to form the anterior chamber;there was no IOL incarceration or displacement or iris prolapse.Conclusion The improved trapezoidal transparent corneal incision can effectively prevent IOL displacement caused by anterior chamber collapse during cataract surgery while ensuring the stability of the anterior chamber.It can also reduce the related complications caused by the watertight incision using a flushing needle and restore patients'vision as early as possible.

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