1.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.
2.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.
3.Lipidomics Combined with Machine Learning for Screening Biomarkers of Early-Stage Lung Cancer in the Elderly
Qing WANG ; Yue HE ; Xu LIU ; Zifan LI ; Kezhong CHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(3):652-662
Based on plasma lipidomics combined with machine learning approaches, this study aimed to screen molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients and to evaluate their diagnostic performance. This was a retrospective diagnostic study consisting of two parts. The first part involved molecular biomarker screening. Elderly patients with early-stage lung cancer (early lung cancer group), patients with benign pulmonary nodules (benign nodule group), and contemporaneous healthy individuals undergoing physical examinations (healthy control group) were enrolled from Peking University People's Hospital between November 2023 and November 2024. In addition, early-stage lung cancer patients and healthy controls meeting the inclusion criteria from a previous study of our research group were included as an independent validation cohort. Plasma samples were collected from all subjects, and untargeted lipidomics analysis was performed using high-performance liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate metabolic differences between groups. L1-regularized support vector machine combined with incremental feature selection was employed to screen diagnostic biomarkers for early-stage lung cancer. Model performance was assessed using receiver operating characteristic curves, calibration curves, Brier scores, and decision curve analysis. The second part involved functional validation of the molecular biomarkers using the human lung adenocarcinoma cell line A549, with palmitoylcarnitine (CAR 16∶0) selected as a representative biomarker for functional validation via CCK-8 and cell scratch assays. A total of 36 patients in the early lung cancer group, 35 patients in the benign nodule group, and 41 healthy controls were enrolled, along with an independent validation cohort of 110 individuals (59 patients with early-stage lung cancer and 51 healthy controls). The principal component analysis results demonstrated that quality control samples were tightly aggregated at the centroid of all samples, reflecting robust instrument performance and dependable data quality.Orthogonal partial least squares discriminant analysis revealed significant metabolic differences between the early lung cancer group and the control group (benign nodule group + healthy control group) (R2X=0.406, R2Y=0.529, Q2Y=0.44). L1-regularized support vector machine identified five carnitine-related lipids-palmitoleoylcarnitine(CAR 16∶1), palmitoylcarnitine, The five plasma carnitine-related lipids screened based on untargeted lipidomics and machine learning may serve as potential molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients. The high-sensitivity characteristic of the model makes it particularly suitable for screening scenarios in early-stage lung cancer.
4.Randomized Controlled Clinical Observation on the Treatment of Lumbar Disc Herniation of Cold-Dampness Obstruction Type with Hot Ironing of Haitongpi Formula (海桐皮方) Combined with Three Movements Technique of Qinggong Spinal Manipulation
Fajie LI ; Yue ZHANG ; Tianhao WAN ; Manhong YANG ; Di XIA ; Qing ZHANG
Journal of Traditional Chinese Medicine 2025;66(10):1023-1030
ObjectiveTo observe the clinical efficacy and safety of hot ironing with Haitongpi Formula (海桐皮方, HF) in the treatment of lumbar disc herniation (LDH) of cold-dampness obstruction type. MethodsA total of 70 patients with cold-dampness obstruction type LDH were randomly divided into a treatment group and a control group, with 35 cases in each group. Both groups received three movements technique of Qinggong Spinal Manipulation (QSM) as the basis for treatment. In addition, the treatment group received hot ironing with HF, while the control group applied Diclofenac Sodium Gel externally. The treatment duration for both groups was 14 days. The clinical efficacy was compared between groups. Japanese Orthopedic Association (JOA) score, visual analog scale (VAS) for pain, pain pressure threshold (PPT) for lumbar positive response points, and traditional Chinese medicine (TCM) symptom scores were compared, on day 7, and day 14 of treatment, as well as on day 7 and day 14 of follow-up. The lumbar curvature index (LCI) was also compared before treatment and on day 14 of treatment. Adverse reactions during the study were recorded for both groups. ResultsA total of 35 patients in the treatment group and 34 patients in the control group were included for final analysis. The clinical total effective rate of the treatment group (91.43%, 32/35) was significantly higher than that of the control group (82.35%, 28/34, P<0.05). Both the JOA score and PPT of the two groups increased on day 7 and day 14 of treatment, and on day 7 and day 14 of follow-up. VAS scores and TCM symptom scores both decreased. The LCI of both groups increased on day 14 of treatment (P<0.01). Compared with the control group at the same time points, on day 14 of treatment and day 7 and day 14 of follow-up, the treatment group had higher JOA scores and PPT, and lower VAS scores and TCM symptom scores. The LCI of the treatment group increased on day 14 of treatment (P<0.05 or P<0.01). One case in the control group showed mild skin allergy, with no other adverse reactions observed in either group. ConclusionBased on three movements technique of QSM, hot ironing with HF shows better clinical efficacy than external Diclofenac Sodium Gel in the treatment of cold-dampness obstruction type LDH. It can significantly reduce lumbar pain, increase pain pressure threshold, improve clinical symptoms, lumbar function, and lumbar curvature, with good safety.
5.Selenium nanoparticles synthesized by Streptomyces avermitilis: physical and chemical characteristics and inhibitory activity on a pathogen of Lycium barbarum.
Qi ZHANG ; Yani LI ; Rongjuan ZHOU ; Jiayuan QING ; Sijun YUE
Chinese Journal of Biotechnology 2025;41(2):693-705
Biosynthesized selenium nanoparticles (SeNPs) have attracted much attention because of their unique physical, chemical, and biological properties. The microbial reduction of selenium salts to SeNPs has great potential, while there is a lack of elite strains. In this study, we explored the reduction of Na2SeO3 by Streptomyces avermitilis into SeNPs. The colonies and hyphae of the strain and the synthesized SeNPs were characterized by optical microscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). At the same time, the inhibitory activity of SeNPs on Fusarium oxysporum, the main pathogen causing root rot of Lycium barbarum, was studied. The results showed that S. avermitilis converted Na2SeO3 into SeNPs and tolerated 300 mmol/L Na2SeO3, demonstrating strong tolerance. S. avermitilis synthesized spherical SeNPs in the cytoplasm, and most of SeNPs had a diameter of about 100 nm and were released by hyphal fracture. The SeNPs synthesized by S. avermitilis were amorphous, and their surfaces were dominated by C and Se, with the existence of O, N and other elements. SeNPs had functional groups such as -OH, C=O, C-N, and C-H, which were closely related to the stability and biological activity of SeNPs. The SeNPs synthesized by S. avermitilis showcased significant inhibitory activity on F. oxysporum, and 25.0 μmol/mL SeNPs showcased the inhibition rate of 77.61% and EC50 of 0.556 μmol/mL. In conclusion, S. avermitilis can tolerate high Na2SeO3 stress and mediate the synthesis of SeNPs. The synthesized SeNPs have good stability and strong inhibitory activity, demonstrating the potential application value in the preparation of SeNPs and the control of L. barbarum root rot.
Streptomyces/metabolism*
;
Fusarium/drug effects*
;
Lycium/microbiology*
;
Selenium/metabolism*
;
Nanoparticles/chemistry*
;
Plant Diseases/microbiology*
;
Metal Nanoparticles/chemistry*
;
Antifungal Agents/pharmacology*
6.Research Progress in Application of Sensory Stimulation Therapy in Patients With Alzheimer's Disease.
Pan LIU ; Yue ZHANG ; Qing-Hui MENG
Acta Academiae Medicinae Sinicae 2025;47(4):621-627
As population aging aggravates,the prevalence of dementia is increasing,seriously impacting the daily lives of patients.Sensory stimulation therapy has emerged as a safe and effective non-pharmacological intervention for individuals with dementia.Consequently,exploring non-pharmacological treatments for Alzheimer's disease is crucial.By a review of the relevant literature,this paper provides an overview of sensory stimulation therapy in terms of the concept,applications,and effects on dementia,aiming to promote the broader implementation of this therapy in the care of individuals with dementia.
Humans
;
Alzheimer Disease/therapy*
7.Rapid On-site Analysis of Four Prohibited Sex Hormones in Cosmetics Using Online Derivatization Reaction and A Miniature Mass Spectrometer
Li-Li TONG ; Yan-Hong HU ; Ren-You YANG ; Yue-Guang LYU ; Yu-Han SHANG ; Qing LYU ; Qing ZHANG ; Qiang WANG ; Xiang-Yu GUO
Chinese Journal of Analytical Chemistry 2025;53(10):1623-1630
Due to the poor ionization efficiency and the weak mass spectrometry(MS)intensity of weakly polar substances,direct analysis using the traditional electrospray ionization mass spectrometry(ESI-MS)is a big challenge.In this study,a novel rapid on-site detection method of four prohibited sex hormones in cosmetics was proposed using online derivatization strategy coupled with a miniature mass spectrometer.The target substances in the samples were extracted by a custom-made polyaniline/multi-walled carbon nanotube solid-phase microextraction(SPME)probe.The stirring speed was 200 r/min,the extraction temperature was 40℃,and the extraction time was 2 min.A pulled dual-channel θ borosilicate glass capillary emitter was used as the nano-ESI ion source.The SPME probe was inserted into the channel containing methanol in theθborosilicate glass capillary.When the spray voltage was applied,the four sex hormones were desorbed and formed spray microdroplets,which then collided with the hydroxylamine microdroplets generated from the other channel.The microdroplets of reaction product entered into the miniature mass spectrometer for direct analysis.The limits of detection(LOD)and limits of quantification(LOQ)for the four sex hormones were 10-20 ng/mL and 20-50 ng/mL,respectively.The recoveries were from 84.6%to 107.8%with the relative standard deviations(RSD)from 4.1%to 11.6%.Compared to detection without derivatization,the MS signals of the four target substances were increased by 3 to 15 times.This method was simple,rapid,highly efficient and sensitive,and suitable for on-site rapid analysis of weakly polar sex hormones in cosmetics.
8.Clinical efficacy comparison of ileal conduit,flap embedding method,and traditional cutaneous ureteros-tomy in patients with bladder cancer
Xufeng YU ; Meimian HUA ; Shuxiong ZENG ; Wei HE ; Ziwei WANG ; Qing CHEN ; Chen ZHANG ; Yue WANG ; Yi WANG ; Chuanliang XU
The Journal of Practical Medicine 2025;41(10):1517-1524
Objective To compare the clinical efficacy of different urinary diversions,specifically exploring whether the flap embedding technique can improve bladder cancer patients'quality of life and reduce the incidence of related complications.Methods 63 bladder cancer patients undergoing radical cystectomy with urinary diver-sion,between December 2022 and December 2023,were divided into three groups:Ileal conduit group(n=21),flap embedding technique group(n=21),and traditional cutaneous ureterostomy group(n=21).General clini-cal data,surgical data,preoperative and postoperative renal function indicators,incidence of complications within 6 months postoperatively,and quality of life scores were compared among the groups.Results The operative time in the ileal conduit group was longer than that in the other two groups(P<0.05).The quality of life scores in the flap embedding technique group were superior to those in the traditional cutaneous ureterostomy group(P<0.05),but no significant difference was found compared to the ileal conduit group(P>0.05).In terms of postoperative complications,the incidence of intestinal obstruction in the flap embedding technique group was lower than that in the ileal conduit group(P<0.05),and the rate of reinsertion of a single-J stent for hydronephrosis in the flap embedding technique group was lower than that in the traditional cutaneous ureterostomy group(P<0.05).Postop-erative serum creatinine levels in the traditional cutaneous ureterostomy group were significantly higher than preop-erative levels(P<0.05),while no significant differences in renal function indicators were observed in the other two groups(P>0.05).Conclusion The flap embedding technique significantly improves patients'quality of life and reduces the incidence of postoperative complications.It is worthy of further promotion in clinical practice.
9.Adrenal crisis caused by combination chemotherapy with vincristine, etoposide, and carboplatin in a child
Adverse Drug Reactions Journal 2025;27(6):372-374
A 5-year-old male patient with congenital adrenal hyperplasia and 21 hydroxylase deficiency was treated with intervention, laser, left eye retinoblastoma resection, and retinal repositioning surgery for left eye retinoblastoma at the age of 2 years and 3 months. At the age of 3 years and 4 months, the child underwent peritoneal tumor resection and partial adrenalectomy for adrenal neuroblastoma. Hydrocortisone 2.5 mg thrice daily orally and fludrocortisone 0.02 mg once daily orally were given regularly for a long time after surgery. Three years after the resection of the left eye retinoblastoma, the tumor recurred and the child underwent another resection and retinal retinal repositioning surgery for the left eye retinoblastoma. After the surgery, he received a combination chemotherapy of vincristine (1.06 mg by intravenous infusion on day 1), etoposide (105 mg by intravenous infusion on days 1-2), and carboplatin (395 mg by intravenous infusion on day 1) (VEC) for left retinoblastoma, with 28 days as one treatment cycle. After 2 days of medication, the child experienced nausea, vomiting, and abdominal discomfort. After 5 days, he developed pale complexion, nausea, vomiting, and poor mental state. Laboratory tests showed cortisol 29.6 μg/L, blood sodium 133 mmol/L, and random blood glucose 2.4 mmol/L. Adrenal crisis caused by VEC chemotherapy was considered. Oral hydrocortisone was stopped and switch to intravenous infusion of hydrocortisone 10 mg thrice daily, while symptomatic treatment such as sodium supplementation was given. After 2 days, the symptoms of the child were improved. After 7 days, the child had no nausea or vomiting, cortisol increased to 291.0 μg/L, and blood sodium and blood glucose returned to normal.
10.Predictive value of dose surface histogram for acute radiation proctitis induced by image guided radiotherapy for cervical cancer
Qing-xiao LIU ; Yue-xiang ZHU ; Wei WEI ; Long TIAN ; Song-lin YANG ; Zheng WANG ; Yu-sen ZHAO ; Su-li WANG ; Mao-ye CHANG
Chinese Medical Equipment Journal 2025;46(3):48-53
Objective To explore the predictive value of dose surface histogram(DSH)in image guided radiotherapy(IGRT)for radiotherapy-induced acute radiation proctitis(ARP)in cervical cancer(CCA).Methods Totally 380 patients with CCA IGRT admitted to some hospital from May 2019 to May 2023 were selected prospectively and randomly divided into a control group(n=1 80)and an experimental group(n=200).The patients in the 2 groups were followed up and the incidence rates of ARP were counted,and rectal dose distribution was evaluated using dose volume histogram(DVH)in the control group and DSH in the experimental group.The predictive values of DVH and DSH for ARP were evaluated and compared using ROC curves.Statistical analysis was performed using SPSS 21.0 software.Results The two groups did not have statistically significant difference in the incidence rate of ARP(P>0.05),while there were significant differences in the evaluation indicators of the rectal dose distribution(P<0.05).V40,V50,S40 and S50 proved to have low predictive values for grade Ⅰ-Ⅳ ARP with AUC 0.700(P<0.05);V60 and S60 had moderate predictive values for grade Ⅰ-Ⅳ ARP with AUC greater than 0.700 and less than or equal to 0.900(P<0.05);V70,V78,S70 and S7s showed high predictive values for grade Ⅰ-Ⅳ ARP with AUC higher than 0.900(P<0.05).Delong's test results indicated that DVH and DSH had no significant differences in AUC when used to predict gradeⅠ-Ⅳ ARP(allP>0.05).Conclusion DSH is essentially the same as DVH when used for the prediction of grade Ⅰ-Ⅳ ARP due to CCA IGRT,and thus can be used for the supplementation and optimization of radiotherapy planning systems.[Chinese Medical Equipment Journal,2025,46(3):48-53]

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