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.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
4.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
5.Effect of Wenyang Huazhuo Formula (温阳化浊方) on Reproductive Aging,Ovarian Mechanical Micro-environment,and Offspring Reproductive Potential in Aged Model Mice
Jiaqi XU ; Xiaoli ZHAO ; Nan JIANG ; Kaixi LI ; Yafei DING ; Zimu WEN ; Yingying JIA ; Mengjun JIANG ; Tian XIA
Journal of Traditional Chinese Medicine 2025;66(6):612-620
ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula (温阳化浊方, WHF) in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups, 3-month group (20 female mice at 3 months of age), 6-month group (20 female mice at 6 months of age), 6-month + WHF group (20 female mice at 5 months of age treated with WHF), 9-month group (20 female mice at 9 months of age), and 9-month + WHF group (20 female mice at 8 months of age treated with WHF). The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/(kg·d) once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid (HA) content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained, as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group, the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), decreased ovarian collagen content, and reduced numbers of primordial and secondary follicles. In contrast, the numbers of primary follicles, antral follicles, and atretic follicles increased. The levels of anti-Müllerian hormone (AMH), ovarian HA content, and the fertilization rate, cleavage rate, and blastocyst formation rate of oocytes from offspring were significantly lower (P<0.05). Compared with the 6-month group, the 6-month + WHF group showed significantly reduced serum levels of GnRH, FSH, and LH, with a significant decrease in primary follicles, antral follicles, and atretic follicles as well as increase of AMH levels, ovarian HA content, number of primordial and secondary follicle, egg count, and offspring birth weight (P<0.05). Compared with the 9-month group, the 9-month + WHF group exhibited reduced GnRH, FSH, and collagen fiber content, as well as reduced number of primary follicles, antral follicles, and atretic follicles. However, AMH levels, ovarian HA content, number of primordial and secondary follicle, egg count, offspring numbers, birth weight, fertilization rate, cleavage rate, and blastocyst formation rate of oocytes from offspring all significantly increased (P<0.05). ConclusionWHF can significantly improve the ovarian reserve, fertility, and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover, the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.
6.Impact of pathological aging of the endometrium on embryo implantation
Yingying JIA ; Xiaoli ZHAO ; Jiaqi XU ; Nan JIANG ; Zimu WEN ; Kaixi LI ; Tian XIA
Chinese Journal of Reproduction and Contraception 2025;45(5):462-467
Decreased endometrial receptivity is a critical factor contributing to the decline in fertility among women of advanced age. With the increase of age, the endometrium exhibits diminished hormonal responsiveness, a phenomenon known as inflammaging, and an imbalance in immune cell populations. These changes impede the processes of endometrial epithelial-mesenchymal transition and decidualization, thereby negatively impacting embryo implantation and reducing overall fertility potential. Furthermore, adverse lifestyle choices, exposure to environmental factors, inflammatory conditions, and repeated interventions within the uterine cavity can result in pathological aging of the endometrium that does not align with its chronological age. This misalignment may be associated with the emergence of various reproductive disorders, even in younger women. This paper seeks to investigate the relationship between pathological aging of the endometrium and reproductive disorders, particularly in the context of embryo implantation, with the aim of providing new insights into the pathogenesis, clinical diagnosis, and treatment of reproductive disorders.
7.Impact of Wenyang Huazhuo Formula on spontaneous pregnancy outcomes in advanced-age infertile patients with spleen-kidney yang deficiency syndrome
Jiaqi XU ; Xiaoli ZHAO ; Zimu WEN ; Yingying JIA ; Tian XIA
Chinese Journal of Reproduction and Contraception 2025;45(11):1113-1118
Objective:To evaluate the therapeutic efficacy of the Wenyang Huazhuo Formula on spontaneous pregnancy outcomes in advanced-age infertile patients with spleen-kidney yang deficiency syndrome.Methods:A retrospective cohort study design was employed to gather clinical data from 303 advanced-age infertile patients with spleen-kidney yang deficiency syndrome who sought treatment at the Department of Reproductive Medicine in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between June 2019 and June 2023. Patients were categorized into two groups based on their treatment regiments: a basic treatment group (non-exposed group, n=151) and a group receiving basic treatment in conjunction with the Wenyang Huazhuo Formula (exposed group, n=152). The study compared and analyzed pregnancy outcomes, including time to pregnancy (TTP) within one year, ongoing pregnancy rate, and clinical pregnancy rate, between the two groups over a one-year follow-up period. Additionally, stratified analyses were performed based on age and anti-Müllerian hormone (AMH) levels to evaluate the impact of Wenyang Huazhuo Formula on pregnancy outcomes across different patient subgroups. Results:The TTP in the exposed group was significantly reduced compared with the non-exposed group ( HR=1.70, 95% CI: 1.12-2.57, P=0.013), suggesting a significant shortening of their TTP, and the ongoing pregnancy rate [28.29% (43/152)] and the clinical pregnancy rate [33.55% (51/152)] were significantly higher than those in the non-exposed group [13.91% (21/151), P=0.020; 21.85% (33/151), P=0.023], and the early abortion rate [15.69% (8/51)] was significantly reduced compared with the non-exposed group [36.36% (12/33), P=0.031]. Stratified analyses by age revealed that for patients aged 35-37 years, the exposed group exhibited a significantly shorter TTP ( HR=1.67, 95% CI: 1.03-2.70, P=0.038), while no significant difference in TTP was observed in the 38-44-year old patients ( HR=1.78, 95% CI: 0.77-4.10, P=0.174). Regarding the ongoing pregnancy rate, the exposed group showed a significant higher rate [31.31% (31/99)] than the non-exposed group [13.91% (15/112), P=0.022] among patients aged 35-37 years, whereas no significant difference was observed in the 38-44 years old group ( P=0.386). Stratified analysis based on AMH levels showed that both low AMH levels (<1.68 μg/L) and high AMH levels (≥1.68 μg/L) patients in the exposed group experienced a significant reduction in TTP compared with the non-exposed group ( HR=8.07, 95% CI: 1.04-62.52, P=0.046; HR=1.57, 95% CI: 1.01-2.43, P=0.044, respectively), along with a notable improvement in the ongoing pregnancy rate [13.64% (6/44) vs. 0% (0/29), P=0.038; 34.26% (37/108) vs.17.21% (21/122), P=0.028, respectively]. Further stratified analysis indicated that, compared with patients with low AMH levels, both the exposed group and the non-exposed group of patients with high AMH levels exhibited a significantly shorter TTP ( HR=1.91, 95% CI: 1.02-3.69, P=0.043; HR=9.48, 95% CI: 1.30-69.22, P=0.002, respectively), along with a significantly higher ongoing pregnancy rate ( P=0.014; P=0.008). Conclusion:The Wenyang Huazhuo Formula significantly shortens TTP, enhances both the clinical pregnancy rate and the ongoing pregnancy rate and reduces the early abortion rate in advanced-age infertile women diagnosed with spleen-kidney yang deficiency syndrome.
8.Analysis of correlation between ankle instability and load-induced osteochondral lesions of the talus
Yubo XIA ; Ying GUO ; Wen LUO ; Zhen SHEN ; Ziliang RUAN ; Miao TIAN ; Tao WANG ; Wei DONG
Chinese Journal of Trauma 2025;41(2):169-176
Objective:To investigate the biomechanical correlation between ankle instability and osteochondral lesions of the talus (OLT) under loading conditionsMethods:A healthy 29-year-old male volunteer was selected for the study. A 64-slice spiral CT scan of the right lower limb was performed to construct a detailed finite element model of the ankle joint, including ligaments and cartilage. Three injury models were created: models of distal tibiofibular syndesmosis injury, lateral collateral ligament injury, and a combined injury of the distal tibiofibular syndesmosis and lateral collateral ligament. Differences in stress distribution on the tibiotalar joint surface, talus stress, and talus displacement were analyzed through anterior drawer test, inversion stress test, and external rotation stress test.Results:In the anterior drawer test, as the forward traction force increased (40, 60, 80, 100, 120, 140, and 150 N), all the injury models showed a progressive increase in tibiotalar joint surface stress, talus stress, and talus displacement. The combined injury model showed the highest tibiotalar joint surface stress (32.6 MPa), while the lateral collateral ligament injury model demonstrated the highest talus stress (56.5 MPa). Talus displacement increased significantly with traction, reaching the maximum (4.88 mm) in the combined injury model under 150 N. In the inversion stress test, stress on the tibiotalar joint surface in the lateral collateral ligament injury model was concentrated on the posterior-lateral and posterior-medial regions, whereas in the combined injury model, stress on the tibiotalar joint surface was predominantly concentrated in the posterior-medial region. Talus stress was localized to the talus neck and body in all the models, with the combined injury model showing the largest talus displacement (8.46 mm). In the external rotation stress test, stress on the tibiotalar joint surface was mainly distributed in the posterior-medial, posterior-lateral, and anterior-lateral regions in all the models. Talus stress was concentrated at the talus neck and body. The combined injury model exhibited the greatest talus displacement (12.50 mm).Conclusion:Ankle instability, particularly from combined injuries of the distal tibiofibular syndesmosis and lateral collateral ligament, significantly increases the stress concentration and talus displacement under loading conditions, thus elevating the risk of OLT.
9.Advances in the use of human respiratory stem cells in the treatment of respiratory tract infections
Xuan LIU ; Wenyan TIAN ; Ze CHEN ; Yingli QU ; Jin CAO ; Chenxi ZHANG ; Qi WEN ; Qin LUO ; Qiangqiang SHI ; Lifeng ZHANG ; Guoyong MEI ; Haijun DU ; Zhiqiang XIA ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(1):128-132
Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.
10.Effect and mechanism of alkaloids from Portulacae Herba on ulcerative colitis in mice based on TLR4/MyD88/NF-κB signaling pathway.
Jia-Hui ZHENG ; Ying-Ying SONG ; Tian-Ci ZHANG ; Wen-Ting WANG ; Zhi-Ping YANG ; Jin-Xia AI
China Journal of Chinese Materia Medica 2025;50(4):874-881
This study investigated the functions and regulatory mechanism of Portulacae Herba and its chemical components on the Toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MyD88)/nuclear factor kappa B(NF-κB) inflammatory signaling pathway in the colon tissue of mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC). A total of 35 mice were randomly divided into groups, including a blank group, a model group, a mesalazine group(0. 5 g·kg~(-1)), and low, medium,and high dose alkaloids from Portulacae Herba groups(9, 18, 36 mg·kg~(-1)), and a combination treatment group, with 5 mice in each group. The blank group was given purified water, while the other groups were continuously given a 3% DSS solution for 7 days to induce the UC model. From day 8 onwards, the treatment group received oral gavage according to the prescribed doses for 14 days. The overall condition, body weight, stool characteristics, and presence of blood in the stool were recorded daily. After the experiment, the disease activity index(DAI) was assessed for each group, and colon length was measured. Histopathological changes in colon tissue were examined using hematoxylin-eosin(HE) staining. The levels of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α),and interleukin-1β( IL-1β) in serum were measured by enzyme-linked immunosorbent assay( ELISA). The protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were measured using Western blot and quantitative real-time PCR(qPCR).Compared to the blank group, the model group showed a significant decrease in body weight, a notable increase in DAI scores, a significant shortening of colon length, and evident histopathological damage. The levels of inflammatory cytokines TNF-α and IL-1β in the serum were significantly elevated, and the protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were significantly up-regulated. In contrast, the alkaloids from Portulacae Herba treatment groups significantly improved symptoms and reduced body weight loss in mice, decreased DAI scores, alleviated colon shortening, lowered serum levels of TNF-α and IL-1β,significantly down-regulated the expression levels of TLR4, MyD88, and NF-κB proteins and genes in colon tissue, as well as reduced histopathological damage. Therefore, the study suggests that alkaloids from Portulacae Herba can alleviate intestinal inflammation damage in DSS-induced UC mice, with its mechanism involving the TLR4/MyD88/NF-κB signaling pathway.
Animals
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Colitis, Ulcerative/immunology*
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Toll-Like Receptor 4/immunology*
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Myeloid Differentiation Factor 88/metabolism*
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Mice
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NF-kappa B/metabolism*
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Signal Transduction/drug effects*
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Male
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Alkaloids/administration & dosage*
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Drugs, Chinese Herbal/administration & dosage*
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Humans
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Female
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Colon/metabolism*
;
Disease Models, Animal

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