1.Comparative Study on Effect of Jingui Shenqiwan and Liuwei Dihuangwan on Reproductive Ability and Brain Function of Normal Mice
Hong SUN ; Fan LEI ; Chenggong LI ; Rui LUO ; Shixian HU ; Bin REN ; Juan HAO ; Yi DING ; Lijun DU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):1-14
ObjectiveTo explore the effects of Jingui Shenqiwan (JSW) and Liuwei Dihuangwan (LDW) on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group, the other six groups were as follows: a group of both males and females receiving JSW (3.0 g·kg-1), a group of both males and females receiving LDW (4.5 g·kg-1), a group of males receiving water and females receiving JSW, a group of males receiving water while females receiving LDW, a group of females receiving water while males receiving JSW, and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 (female∶male) ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth, which was followed by the observation of newborn mice, calculation of their average number, and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment, the weights of the thymus and spleen were measured to calculate the organ coefficients, and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems, while novel object recognition test (NOR) was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction (Real-time PCR) assay, and protein expression was analyzed with Western blot. ResultsCompared with the control group, oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together (P<0.05), while LDW showed a trend but no statistical significance. Additionally, compared with the control group, JSW could upregulate the gene expression of gonadotropin-releasing hormone (GnRH) in the thalamus, as well as reproductive stem cell factor (SCF) and tyrosine kinase receptor (c-Kit) in the testes and reproductive stem cell marker mouse vasa homologue (MVH) in the ovaries, upregulate the expression of proteins influencing neuronal functional activity, such as brain-derived neurotrophic factor (BDNF), in hippocampal neurons (P<0.05), and enhance sucrose preference in male mice (P<0.05). Compared with the control group, JSW significantly increased sucrose preference and novel object recognition index in offspring mice (P<0.05), which was related to the upregulation of hippocampal dopamine D1 receptor (D1R) and N-methyl-D-aspartate receptor (Nmdar) gene expression. Compared with the control group, both JSW and LDW could upregulate the protein expression of glucocorticoid receptor (GR), BDNF, and tyrosine kinase receptor B (TrkB) in the hippocampus of offspring mice (P<0.05). ConclusionJSW significantly enhances the reproductive ability of normal mice, which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally, JSW has a certain regulatory effect on the brain function of the offspring mice.
2.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
3.Diagnosis and Treatment of Chronic Heart Failure Based on Thinking of Five Differentiation
Kun LIAN ; Lichong MENG ; Manting YI ; Lin LI ; Fei WANG ; Siyuan HU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):160-168
Chronic heart failure (CHF) refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium, resulting in reduced pumping and/or filling functions of the heart. In recent years, the mechanisms, pathways, and targets of traditional Chinese medicine (TCM) in the treatment of CHF have been continuously confirmed, and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM, Professor LI Candong innovatively proposed the thinking of five differentiation: Disease differentiation, syndrome differentiation, pathogenesis differentiation, symptom differentiation, and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking, emphasizing comprehensive syndrome differentiation, objective analysis, dynamic assessment, and individualized treatment. In terms of diagnosis, the first is to identify the disease name, cause, location, severity, and type of CHF, determine the type and its evolution, and clarify the process of transmission and transformation between deficiency and excess. Secondly, it is necessary to distinguish the authenticity, severity, primary and secondary, urgency and complexity of CHF syndromes, providing scientific guidance for syndrome differentiation and treatment. Thirdly, according to the symptoms and the principles of deficiency and excess, the physician should identify the core pathogenesis of CHF from the perspectives of Qi, blood, Yin, Yang, deficiency, stasis, phlegm, water, and toxins. Fourthly, from the macro, meso and micro levels, the physician should carefully distinguish the presence or absence, severity, authenticity, and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally, personalized medication for CHF should be promoted based on the patient's gender, age, constitution, and living habits. In terms of treatment, based on the thinking of five differentiation, we propose that the treatment of CHF should integrate the disease and syndrome, clarify the pathogenesis, and apply precise treatment. The treatment should be people-oriented, staged, and typed, and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment, and combines the three causes for appropriate treatment, providing new ideas and insights for the diagnosis and treatment of CHF.
4.Differences in chemical components and quality analysis of Gardenia jasminoides before and after processing with ginger
Lihua TANG ; Yu WU ; Xuedi HUANG ; Xiaolian HU ; Yi TANG ; Zilong CHEN ; Xiaofan XIAO ; Xide YE
China Pharmacy 2026;37(2):168-173
OBJECTIVE To analyze the differences in chemical components of Gardenia jasminoides before and after processing with ginger, and to evaluate the quality differences among different producing areas. METHODS Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry was used to analyze the compositional differences of G. jasminoides before and after processing with ginger. The water content, total ash, and ethanol-soluble extract content of ginger- processed G. jasminoides were determined according to the 2020 edition of Chinese Pharmacopoeia. High performance liquid chromatography was adopted to determine the contents of genipin gentiobioside, geniposide, crocin Ⅰ and crocin Ⅱ in ginger- processed G. jasminoides. RESULTS A total of 49 chemical components were identified from raw G. jasminoides and ginger- processed G. jasminoides, including 14 flavonoids, 15 iridoids, 10 organic acids, 2 alkaloids and 8 other compounds. Among them, 42 components were detected in raw G. jasminoides, 28 in ginger-processed G. jasminoides, and 21 components were common to both. After processing with ginger, raw G. jasminoides lost 21 components (including iridoids, flavonoids, alkaloids, and others), while 7 chemical components were added (including coumarins, organic acids, organic acid esters, and flavonoids). For the 15 batches of ginger-processed G. jasminoides, the water content ranged from 5.64% to 7.11%, total ash from 2.92% to 4.87%, and ethanol-soluble extract from 40.61% to 58.02%. The average contents of genipin gentiobioside, geniposide, crocin Ⅰ and crocin Ⅱ were 0.108 7, 0.542 2, 0.565 0, and 0.012 5 mg/g, respectively. CONCLUSIONS After processing with ginger, G. jasminoides loses 21 components, while 7 new components are added. Differences are observed in the water content, total ash, ethanol-soluble extract, and the contents of genipin gentiobioside, geniposide, crocin Ⅰ, and crocin Ⅱ of ginger-processed G. jasminoides from different producing areas. Notably, samples from Fujian exhibit high contents of genipin gentiobioside and ethanol-soluble extract, while samples from Jiangxi have a high content of crocin Ⅰ.
5.Mechanism of pachymic acid in ameliorating renal injury in pregnancy induced hypertension rats by regulating the Sirt1/PGC‑1α pathway
Junjiang ZHU ; Jincheng LIN ; Jiajian WU ; Yi ZENG ; Jun HU ; Min LI ; Hongying LIU ; Jinfen LI
China Pharmacy 2026;37(2):186-191
OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension (PIH) rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α (Sirt1/PGC-1α) pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester (L-NAME) method. PIH rats were randomly divided into model group, L-pachymic acid (low-dose pachymic acid, 10 mg/kg) group, H-pachymic acid (high-dose pachymic acid, 20 mg/kg) group, and H-pachymic acid+EX527 (20 mg/kg pachymic acid+10 mg/kg EX527) group, with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily, once a day, for 28 consecutive days. After the last administration, 24 h urinary protein and tail artery systolic blood pressure (SBP) were measured in pregnant rats from each group, along with the levels of serum creatinine (Scr), blood urea nitrogen (BUN),uric acid (UA), and cystatin C (Cys-C). The contents of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in renal tissue, as well as the mRNA and protein expression levels of Sirt1 and PGC-1α, were also determined. Meanwhile, renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. RESULTS Compared with model group, L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification, tail artery SBP, Scr, BUN, UA, Cys-C levels, glomerulosclerosis index score of renal tissue, renal tubular injury score, the percentage of PAS positive area, MDA and 8-OHdG (P<0.05). Conversely, the contents of SOD and GSH-Px, along with the mRNA and protein expression levels of Sirt1 and PGC-1α, were significantly increased (P<0.05). Moreover, these improvements were more pronounced in H-pachymic acid group (P<0.05). Compared with H-pachymic acid group, the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal (P<0.05). CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats, potentially through activation of the Sirt1/PGC-1α pathway.
6.Application of AI versus Mimics software for three-dimensional reconstruction in thoracoscopic anatomic segmentectomy: A retrospective cohort study
Chengpeng SANG ; Yi ZHU ; Yaqin WANG ; Li GONG ; Bo MIN ; Haibo HU ; Zhixian TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):313-321
Objective To analyze the application effects of artificial intelligence (AI) software and Mimics software in preoperative three-dimensional (3D) reconstruction for thoracoscopic anatomical pulmonary segmentectomy. Methods A retrospective analysis was conducted on patients who underwent thoracoscopic pulmonary segmentectomy at the Second People's Hospital of Huai'an from October 2019 to March 2024. Patients who underwent AI 3D reconstruction were included in the AI group, those who underwent Mimics 3D reconstruction were included in the Mimics group, and those who did not undergo 3D reconstruction were included in the control group. Perioperative related indicators of each group were compared. Results A total of 168 patients were included, including 73 males and 95 females, aged 25-81 (61.61±10.55) years. There were 79 patients in the AI group, 53 patients in the Mimics group, and 36 patients in the control group. There were no statistical differences in gender, age, smoking history, nodule size, number of lymph node dissection groups, postoperative pathological results, or postoperative complications among the three groups (P>0.05). There were statistical differences in operation time (P<0.001), extubation time (P<0.001), drainage volume (P<0.001), bleeding volume (P<0.001), and postoperative hospital stay (P=0.001) among the three groups. There were no statistical differences in operation time, extubation time, bleeding volume, or postoperative hospital stay between the AI group and the Mimics group (P>0.05). There was no statistical difference in drainage volume between the AI group and the control group (P=0.494), while there were statistical differences in operation time, drainage tube retention time, bleeding volume, and postoperative hospital stay (P<0.05). Conclusion For patients requiring thoracoscopic anatomical pulmonary segmentectomy, preoperative 3D reconstruction and preoperative planning based on 3D images can shorten the operation time, postoperative extubation time and hospital stay, and reduce intraoperative bleeding and postoperative drainage volume compared with reading CT images only. The use of AI software for 3D reconstruction is not inferior to Mimics manual 3D reconstruction in terms of surgical guidance and postoperative recovery, which can reduce the workload of clinicians and is worth promoting.
7.In Vitro and in vivo Component Analysis of Total Phenolic Acids from Gei Herba and Its Effect on Promoting Acute Wound Healing and Inhibiting Scar Formation
Xixian KONG ; Guanghuan TIAN ; Tong WU ; Shaowei HU ; Jie ZHAO ; Fuzhu PAN ; Jingtong LIU ; Yong DENG ; Yi OUYANG ; Hongwei WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):156-167
ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba(TPAGH), and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group, recombinant human epidermal growth factor(rhEGF) group(4 mg·kg-1), and low, medium, and high dose groups of TPAGH(3.5, 7, 14 mg·kg-1), with 24 mice in each group. A full-thickness skin excision model was constructed, and each administration group was coated with the drug at the wound site, and the model group was treated with an equal volume of normal saline, the treatment was continued for 30 days, during which 8 mice from each group were sacrificed on days 6, 12, and 30. The healing of the wounds in the mice was observed, and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin(HE), Masson, and Sirius red staining, and enzyme-linked immunosorbent assay(ELISA) was used to dynamically measure the contents of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), vascular endothelial growth factor A(VEGFA), matrix metalloproteinase(MMP)-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH, and molecular docking of key components and targets was performed. Gene Ontology(GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the related targets, so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH, including 28 phenylpropanoids, 31 tannins, 23 triterpenes, 49 flavonoids, and 15 others, and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that, compared with the model group, the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate(P<0.05), and the number of new capillaries, number of fibroblasts, number of new skin appendages, epidermal regeneration rate, collagen deposition ratio, and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved(P<0.05, 0.01), the levels of IL-6, TNF-α, MMP-3 and MMP-9 in the skin tissues were reduced to different degrees, while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets, including tumor protein 53(TP53), sarcoma receptor coactivator(SRC), protein kinase B(Akt)1, signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR) and so on, participating in 75 signaling pathways such as advanced glycation end-products(AGE)-receptor for AGE(AGE/RAGE) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking confirmed that the key components genistein, geraniin, and casuariin had good binding ability to TP53, SRC, Akt1, STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction, thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology, the study explores how key components may bind to targets such as TP53, Akt1 and EGFR, exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.
8.Syndrome Differentiation and Treatment of Atrial Fibrillation based on the Holistic View of "Spleen-Vessels-Heart-Spirit"
Yihang DU ; Chenglin DUAN ; Xueping ZHU ; Meng LYU ; Jiafan CHEN ; Yi WEI ; Yuanhui HU
Journal of Traditional Chinese Medicine 2025;66(1):89-92
Based on the holistic view of "spleen-vessels-heart-spirit" system, this article explores the pathogenesis and progression of atrial fibrillation. It is proposed that the onset of atrial fibrillation is due to failure of the spleen to transport and disharmony of blood vessels; phlegm and blood stasis obstructing the collaterals and damage to the heart structure are the basis of its pathogenesis; the unclear mind and disorder of body and spirit are the causes of its progression. Based on the characteristics of pathological changes in different stages of the disease, it is proposed that early treatment should focus on restoring the middle jiao, clearing and promoting blood vessels, using modified Yigong Powder (异功散); during the progression of the disease, treatment should remove blood stasis and phlegm, nourish heart and protect the pulse, using self-prescribed modified Mengshi Tongmai Decoction (礞石通脉汤); meanwhile, calming mind and stabilizing palpitations, and regulating spirit should be sequentially incorporated, with self-prescribed Jiazao Ningmai Decoction (甲枣宁脉汤) or Shenying Dingji Decoction (参英定悸汤) and modified as appropriate. Clinical treatment should focus on the whole disease course of atrial fibrillation, implementing stage-based treatments to enable early intervention and holistic regulation.
9.Effect of interleukin-8 regulation on monocyte chemotactic protein-1 secretion and expression through the NF-kappaB/p65 signaling pathway on the migration of residual epithelial cells in the lens capsule
Wei SI ; Su XU ; Yuhang ZHANG ; Yi MAO ; Keyu GUO ; Yanzhong HU ; Fengyan ZHANG
International Eye Science 2025;25(4):537-543
AIM: To investigate the effect of interleukin-8(IL-8)on the regulation of monocyte chemotactic protein-1(MCP-1)secreted by lens epithelial cells(LEC)during cell migration in the development of posterior capsule opacification(PCO).METHODS: A rat lens capsule model was established and cultured in medium supplemented with 10% fetal bovine serum. Upon migration of LEC to 30%-50% of the posterior capsule, serum was removed. The capsule was subsequently divided into two groups: a control group and an IL-8(15 ng/mL)treatment group. LEC migration was captured at multiple time points. The secretion and mRNA expression of MCP-1 were quantified using ELISA and RT-qPCR, respectively. Immunofluorescence was used to assess MCP-1 expression in the different experimental groups. SRA01/04 cells were divided into three groups: control, IL-8(15 ng/mL), and IL-8(15 ng/mL)+200 μmol/L Bindarit(BND)groups, with migration measured by the Transwell assay. Additionally, SRA01/04 cells were divided into negative control(NC), NC+15 ng/mL IL-8, and 15 ng/mL IL-8+p65 siRNA groups, and MCP-1 secretion and mRNA expression were further analyzed by ELISA and RT-qPCR.RESULTS:LEC migration in the rat lens capsule cultured in vitro showed that the cells migration of the 15 ng/mL IL-8 group significantly increased at 48, 72 and 96 h(all P<0.05). ELISA results revealed that MCP-1 levels in SRA01/04 cells from the 15 ng/mL IL-8-treated group were markedly higher than those in the control group at both 12 and 24 h(all P<0.05). RT-qPCR analysis also demonstrated a significant increase in MCP-1 mRNA expression in the 15 ng/mL IL-8 group at both time points(all P<0.05). Immunofluorescence staining indicated greater MCP-1 expression in capsular epithelial cells of the 15 ng/mL IL-8 group at 24 h(P=0.007). Transwell assays further confirmed increased cell migration in the 15 ng/mL IL-8 group compared to the control group(P=0.001), while the migration reduced in the 15 ng/mL IL-8+200 μmol/L BND group compared to the 15 ng/mL IL-8 group(P=0.003). Moreover, ELISA and RT-qPCR results demonstrated a significant increase in MCP-1 secretion and mRNA expression in the NC+15 ng/mL IL-8 group at both 12 and 24 h compared to the NC group(all P<0.01). In contrast, MCP-1 secretion and mRNA expression were reduced in the 15 ng/mL IL-8+p65 siRNA group compared to the NC+15 ng/mL IL-8 group at both time points(all P<0.01).CONCLUSION: IL-8 promotes the migration of residual epithelial cells and regulates the secretion and expression of MCP-1 in LEC. The mechanism underlying IL-8's effects appears to be mediated through the activation of the NF-κB/p65 signaling pathway.
10.Therapeutic effect of anti-PD-L1&CXCR4 bispecific nanobody combined with gemcitabine in synergy with PBMC on pancreatic cancer treatment
Hai HU ; Shu-yi XU ; Yue-jiang ZHENG ; Jian-wei ZHU ; Ming-yuan WU
Acta Pharmaceutica Sinica 2025;60(2):388-396
Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8+ to CD4+ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8+ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

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