1.Identification and Biological Characterization of Pathogen and Screening of Effective Fungicides for Wilt of Tetradium ruticarpum
Yuxin LIU ; Qin XU ; Yue YUAN ; Tiantian GUO ; Zheng'en XIAO ; Shaotian ZHANG ; Ming LIU ; Fuqiang YIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):198-206
ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing, investigate there biological characteristics, and screen effective fungicides, so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges, white, short, velvety aerial hyphae, and pale purple undersides. Macroconidia were colorless, sickle-shaped, with 3-5 septa, while microconidia were transparent, elliptical, aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support, which, combined with morphological characteristics, identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar (MBA) with glucose as the carbon source, beef extract and yeast powder as nitrogen sources, 28 ℃, pH 7.0, and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar (PDA) with glucose as the carbon source, beef extract as the nitrogen source, 28 ℃, pH 7.0, and complete darkness. Among chemical fungicides, phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.
2.Syndrome Differentiation and Treatment Mechanisms of Inflammatory Injury in Diabetic Cardiomypathy from Theory of "Gaozhuo"
Xiaoyue WANG ; Yunfeng YU ; Xiangning HUANG ; Yixin XIANG ; Sihao ZHANG ; Qin XIANG ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):235-244
Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM, the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion, and divides the pathological process into three phases: Gaozhuo invasion, turbid heat damage to the channels, and turbid blood stasis and heat junction. Among them, the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors, and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress, it eventually develops into a depletion of the heart Yang, leading to the ultimate regression of heart failure. According to the theory of Gaozhuo, traditional Chinese medicine (TCM) should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause, and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat, strengthening the spleen and tonifying the kidney, and clearing heat and resolving turbidity should be the therapy. If the turbidity, stasis, and heat are knotted in the heart and collaterals, strengthening the spleen and tonifying the kidney, and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity, benefiting Qi and clearing heat to resolve turbidity, and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors, improve the inflammatory damage to myocardium and blood vessels, myocardial fibrosis, and cardiac systole and diastole, and thus slow down the onset and progression of DCM.
3.Analysis of depressive symptoms and associated factors among junior and senior high school students in Beijing from 2019 to 2023
Chinese Journal of School Health 2026;47(1):60-64
Objective:
To investigate the prevalence and associated factors of depressive symptoms among junior and senior high school students in Beijing from 2019 to 2023, in order to provide a scientific basis for interventions targeting high risk groups.
Methods:
From 2019 to 2023, a stratified cluster random sampling method was used to select 88 927 junior and senior high school students from 16 districts in Beijing. The Center for Epidemiologic Studies Depression Scale(CES-D) was conducted to assess depressive symptoms. The Chi square test was used to compare the detection rates of depressive symptoms among different student groups, and the trend Chi square test was employed for trend analysis of detection rates across the years. Multivariate Logistic regression analysis was applied to examine the association between the detection of depressive symptoms and related factors among junior and senior high school students.
Results:
From 2019 to 2023, the prevalence rates of depressive symptoms among junior and senior high school students in Beijing were 20.45%, 18.19%, 16.64%, 17.89% and 18.17%, respectively, with an overall downward trend ( χ 2 trend =27.51, P <0.01). Multivariate Logistic regression analysis revealed that after adjusting for gender, monitoring year, educational stage,family structure,boarding status and has taken a medical leave of absence in the past year unhealthy dietary behaviors ( OR=1.80, 95%CI =1.73-1.87), physical inactivity ( OR=1.24, 95%CI =1.19-1.29), try smoking ( OR=1.46, 95%CI =1.35-1.58), try alcohol( OR=1.96, 95%CI =1.88-2.05), Internet addiction ( OR=3.88, 95%CI =3.57-4.22), and adverse ear related behavior ( OR=1.82, 95%CI =1.71-1.93) were all associated with an increased risk of depressive symptoms among junior and senior high school students (all P <0.05).
Conclusions
The prevalence depression symptoms among middle school students in Beijing showed a fluctuating downward trend from 2019 to 2023. Targeted interventions should be adopted to reduce the occurrence of depression symptoms among junior and senior high school students.
4.Trends of changes in classroom lighting and illumination of primary and secondary schools in Beijing from 2016 to 2023
Chinese Journal of School Health 2026;47(1):134-139
Objective:
To understand the trends of classroom lighting and illumination of primary and secondary schools in Beijing from 2016 to 2023, so as to provide a scientific basis for targeted improvement measures.
Methods:
A sampling survey was conducted on the lighting and illumination indicators of 8 390 classrooms in primary and secondary schools in Beijing from 2016 to 2023. The survey included classroom daylight factor, window to floor area ratio, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards, as well as classroom lighting and blackboard illumination sources. Intergroup comparisons were performed using the Kruskal-Wallis H test and the Chi square test, and Spearman correlation analysis was used to examine the trend of classroom lighting and illumination changes.
Results:
Except the window to floor area ratio, the measured values and compliance rates of all lighting and illumination indicators showed an overall upward trend from 2016 to 2023 (daylight factor r = 0.27, χ 2 trend =206.80, average illuminance on the desk surface r =0.30, χ 2 trend =87.97, illuminance uniformity on the desk surface r =0.14, χ 2 trend =73.59, average illuminance on the blackboard r =0.33, χ 2 trend =477.43, illuminance uniformity on the blackboard r = 0.09, χ 2 trend =50.76) (all P <0.01). The lighting and illumination indicators of classrooms (included classroom daylight factor, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards) in urban schools, primary schools, and secondary schools from 2016 to 2023 showed an upward trend (urban r =0.23-0.40, χ 2 trend =88.66-392.18; primary school r =0.12-0.36, χ 2 trend =39.50-281.44; secondary schools r =0.06-0.31, χ 2 trend =11.79-213.73) (all P < 0.01 ). The illuminance uniformity on the blackboard in suburban schools showed a downward trend ( r = -0.09, χ 2 trend =31.53, both P <0.01). The illuminance uniformity on the desk surface in suburban schools showed no significant change ( r =0.03, χ 2 trend =1.23, both P >0.05). The other indicators showed an upward trend (daylight factor r =0.28, χ 2 trend =40.69, average illuminance on the desk surface r =0.24, χ 2 trend =16.35, average illuminance on the blackboard r =0.25, χ 2 trend =118.05, all P <0.01). The trends of classroom and blackboard illumination sources were that fluorescent lamps decreased year by year and LED lamps increased by year (classroom illumination sources χ 2 trend =1 059.82, blackboard illumination sources χ 2 trend =1 070.25, both P <0.01).
Conclusions
The classroom lighting and illumination in primary and secondary schools in Beijing has shown an overall improving trend from 2016 to 2023. However, problems remain, such as limited improvement of illuminance uniformity indicators, late start and poor effect of reconstruction in suburban schools. Further improvements are still needed.
5.Qualitative and Quantitative Analysis of Chemical Constituents in Gualou Niubangtang by UPLC-Q-TOF-MS/MS and HPLC
Yiyi ZHANG ; Jing YANG ; Yuqing CHENG ; Huimin GAO ; Jin QIN ; Li YAO ; Xiyang DU ; Raorao LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):179-187
ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents, providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem, ChemicalBook, and ChemSpider, combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography (HPLC). ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents, including 69 flavonoids, 36 terpenoids, 23 phenylpropanoids, 8 phenylethanoid glycosides, and 19 other types of constituents. In the established quantitative analysis method, the seven main constituents showed good linearity within their respective linear ranges. The precision, repeatability, stability, and spike recovery all met the required standards. The results showed that the content ranges of geniposide, liquiritin, hesperidin, arctiin, baicalin, oroxylin A-7-O-β-D-glucuronide, and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25, 1.20-7.64, 5.45-7.45, 22.97-33.51, 29.95-39.07, 2.58-4.80, and 6.56-9.31 mg·g-1, respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang, clarifying that its material basis is primarily composed of flavonoids, terpenoids, phenylethanoid glycosides, and phenylpropanoids. Furthermore, it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control, action mechanism, and clinical application of this formula.
6.Quality Evaluation of Gegen Qinlian Tablets Based on HPLC Multi-component Quantification Combined with Chemical Pattern Recognition and TOPSIS Analysis
Ping QIN ; Yingying LU ; Wenming ZHANG ; Zifang FENG ; Lihong GU ; Chenjie XIA ; Minmin HU ; Xiaowei CHEN ; Zhenhua BIAN ; Xiwan LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):217-224
ObjectiveTo establish a high-performance liquid chromatography(HPLC) for the quantitative analysis of multiple components in Gegen Qinlian tablets, and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution(TOPSIS), in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets. MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers, and taking the detection results as variables, SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) to identify key components affecting the quality. Then, TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method. ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation, the method was found to be stable and reliable, and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin, puerarin, 3′-methoxy puerarin, daidzein, coptisine hydrochloride, epiberberine, jatrorrhizine hydrochloride, berberine hydrochloride, palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35, 24.88-42.32, 4.20-9.36, 4.33-7.60, 2.52-6.44, 0.93-4.10, 0.58-3.05, 10.68-22.92, 0.82-4.82, 11.73-60.16 mg·g-1, respectively. Among them, puerarin, berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories, PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%, and OPLS-DA screened out 4 differential markers with variable importance in the projection(VIP) values>1.0, namely baicalin, 3′-hydroxy puerarin, coptisine hydrochloride and palmatine hydrochloride, which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index(Ci) values of different manufacturers were different. Among them, the Ci of manufacturer B was ranked higher, indicating potentially superior quality, while the Ci of manufacturer A was ranked lower, suggesting potentially inferior quality. ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets, and the content uniformity of the same manufacturer is good, while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis, it is found that the content differences of Gegen Qinlian tablets may be related to baicalin, 3′-hydroxy puerarin, coptisine hydrochloride and palmatine hydrochloride.
7.Current status of research on the mechanism of action of emodin in the prevention and treatment of chronic liver diseases
Yajie CHEN ; Xin WANG ; Yunjuan WU ; Ying SU ; Yuhan WANG ; Jinxue ZHANG ; Ning YAO ; Ying QIN ; Xiaoning ZUO
Journal of Clinical Hepatology 2026;42(1):228-234
Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time, resulting in irreversible pathological changes that last longer than 6 months. Emodin (EMO) is a natural anthraquinone derivative derived from Rheum officinale, and its pharmacological effect has been extensively studied, exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases, and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy, EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism, in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.
8.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.
9.Transcriptomic responses of Bulinus globosus to extreme temperature and drought stress
Xinyao WANG ; Dandan PENG ; Ying YANG ; Jianfeng ZHANG ; Zhiqiang QIN ; Kun YANG ; Shizhu LI ; Jing XU
Chinese Journal of Schistosomiasis Control 2026;38(1):29-37
Objective To examine the impact of extreme temperature and drought stress on the survival of Bulinus globosus, so as to provide the theoretical evidence for the genomic research of Bulinus in absence of reference genes. Methods B. globosus snail samples were collected from Kiwani Shehia in Pemba Island, Zanzibar, Tanzania, and offspring snails were obtained through laboratory breeding and reproduction. A total of 120 10-week-old B. globosus snails from the same generation were selected and randomly assigned into four groups, including the high-temperature drought (HD) group, normal temperature drought (D) group, low-temperature drought (LD) group, and the control (C) group, of 30 snails in each group. Snails in HD, D, and LD groups were placed in beakers containing dry soil at the bottom and subsequently housed in climate chambers at 35, 26 ℃, and 10 ℃, respectively, while snails in Group C were maintained in 500 mL petri dishes containing dechlorinated tap water at 26 ℃. Following 3 days of breeding, living snails in each group were collected, and soft tissues were dissected and isolated. Total RNA was extracted from snail soft tissues for library construction, followed by high-throughput sequencing on the Illumina HiSeq 4000 sequencing system. De novo transcriptome assembly was performed using the Trinity software, and the longest transcripts were selected as unigenes. Gene functional annotations of unigenes were conducted using the Diamond software against Gene Ontology (GO) knowledgebase, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, NCBI non-redundant (NR) protein sequences database, Protein Family (Pfam) database, and UniProtKB/Swiss-Prot (Swiss-Prot) knowledgebase. GO and KEGG enrichment analyses of differentially expressed genes (DEGs) were performed using the topGO and clusterProfiler software, respectively. In addition, four relevant genes were selected for validation using a real-time quantitative PCR (qRT-PCR) assay to verify the reliability of transcriptome sequencing results. Results Following 3 days of breeding, there were 7, 20, 28, and 30 survival B. globosus snails in HD, LD, D, and C groups, with corresponding survival rates of 23.33% (7/30), 66.67% (20/30), 93.33% (28/30), and 100.00% (30/30), respectively (χ2 = 52.72, P < 0.001). De novo transcriptome assembly generated 176 942 unigenes, with annotation rates of 0.98%, 13.49%, 26.46%, 12.48%, and 14.39% against GO knowledgebase, KEGG pathway database, NR protein sequences database, Pfam database, and Swiss-Prot knowledgebase, respectively. There were 33 up-regulated and 72 down-regulated genes in Group D, 483 up-regulated and 815 down-regulated genes in Group HD, and 245 up-regulated and 172 down-regulated genes in Group LD relative to in Group C. Following removal of overlapping genes across groups and unmatched genes, 11 candidate genes were identified. GO and KEGG analyses revealed 3 heat shock protein (HSP)-related DEGs in these 11 candidate genes, which were annotated as HSP12.2, HSP70, and HSP20 genes and were all significantly up-regulated in each treatment group. Three immune and nervous system-related DEGs were identified, and were all significantly down-regulated in each treatment group, which were involved in the neural cell adhesion molecule L1-like protein pathway, fibrinogen binding protein pathway, and leukocyte elastase inhibitor-like protein pathway. qRT-PCR assay quantified that the expression trends of four genes related to temperature and drought stress across different treatment groups were highly consistent with transcriptome sequencing data. Conclusion The survival rate of B. globosus significantly reduces under combined stresses of extreme temperature and drought, possibly due to an imbalance in its cellular homeostasis regulatory system.
10.Applications of Lactoferrin and Its Nanoparticles in Cancer Therapy
Wen-Tian YUE ; Shu-Rong HE ; Qin AN ; Yun-Xia ZOU ; Wen-Wen DONG ; Qing-Yong MENG ; Ya-Li ZHANG
Progress in Biochemistry and Biophysics 2026;53(2):342-355
Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.


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