1.Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway.
Mao-Feng ZHONG ; Yu-Jun LUO ; Yu-Yu GUO ; Shuang XIANG ; Wan-Fu LIN
Journal of Integrative Medicine 2025;23(6):683-693
OBJECTIVE:
Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis.
METHODS:
Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.
RESULTS:
In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.
CONCLUSION
JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply*
;
Humans
;
STAT3 Transcription Factor/metabolism*
;
Interleukin-8/metabolism*
;
Liver Neoplasms/blood supply*
;
Aurora Kinase A/metabolism*
;
Neovascularization, Pathologic/drug therapy*
;
Animals
;
Signal Transduction/drug effects*
;
Mice
;
Drugs, Chinese Herbal/therapeutic use*
;
Cell Line, Tumor
;
Mice, Inbred BALB C
;
Mice, Nude
;
Angiogenesis
2.Recent advances, strategies, and future perspectives of peptide-based drugs in clinical applications.
Qimeng YANG ; Zhipeng HU ; Hongyu JIANG ; Jialing WANG ; Han HAN ; Wei SHI ; Hai QIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):31-42
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans
;
Peptides/pharmacology*
;
Animals
;
Neoplasms/drug therapy*
;
Drug Discovery
;
Neurodegenerative Diseases/drug therapy*
;
Diabetes Mellitus/drug therapy*
3.Paclitaxel anti-cancer therapeutics: from discovery to clinical use.
Haizheng YU ; Fen LAN ; Yuan ZHUANG ; Qizhang LI ; Lianqing ZHANG ; Hongchang TIAN ; Xiao BU ; Ruibing CHEN ; Yingying GAO ; Zhuo WANG ; Lei ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):769-789
Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans
;
Paclitaxel/pharmacology*
;
Antineoplastic Agents, Phytogenic/pharmacology*
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Neoplasms/drug therapy*
;
Animals
;
Taxus/chemistry*
4.The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the seventh revision).
Chinese Journal of Internal Medicine 2025;64(12):1155-1168
In 2005, the Chinese Invasive Fungal Infection Working Group published the first guidelines for the diagnosis and treatment of invasive fungal disease (IFD) in patients with hematological disorders and cancers, with the sixth revision released in 2020. Numerous advances in the fields of hematological oncology treatment and the diagnosis and management of IFD have significantly influenced the corresponding strategies. Therefore, the Chinese Invasive Fungal Infection Working Group has reviewed key research advances from 2020 to 2024 and released the seventh revision of the Chinese guidelines. Major revisions include: changes in the epidemiology of IFD; evaluation of novel diagnostic methods (especially PCR and metagenomic next-generation sequencing); updated recommendations on therapeutic drug monitoring and in vitro drug sensitivity test; management of breakthrough IFD; targeted therapy of Pneumocystis jiroveci pneumonia and cryptococcosis; and updated recommendation on the duration of antifungal therapy.
Humans
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Invasive Fungal Infections/drug therapy*
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Hematologic Diseases/complications*
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Antifungal Agents/therapeutic use*
;
Neoplasms/complications*
;
Hematologic Neoplasms/complications*
;
Mycoses/therapy*
;
China
5.Androgen receptor inhibitors in treating prostate cancer.
Ryan N COLE ; Qinghua FANG ; Kanako MATSUOKA ; Zhou WANG
Asian Journal of Andrology 2025;27(2):144-155
Androgens play an important role in prostate cancer development and progression. Androgen action is mediated through the androgen receptor (AR), a ligand-dependent DNA-binding transcription factor. AR is arguably the most important target for prostate cancer treatment. Current USA Food and Drug Administration (FDA)-approved AR inhibitors target the ligand-binding domain (LBD) and have exhibited efficacy in prostate cancer patients, particularly when used in combination with androgen deprivation therapy. Unfortunately, patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer (CRPC). The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification, mutation, and/or splice variants. To effectively inhibit the reactivated AR signaling, new approaches to target AR are being actively explored. These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR. The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
Humans
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Male
;
Androgen Receptor Antagonists/therapeutic use*
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Receptors, Androgen/metabolism*
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Prostatic Neoplasms/drug therapy*
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Prostatic Neoplasms, Castration-Resistant/drug therapy*
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Signal Transduction/drug effects*
6.Sexual activity in men undergoing ADT for localized prostate cancer: a narrative literature review.
Laeticia CREIDY ; Daniel TAUSSKY ; Frederic POULIOT ; Fred SAAD ; Fabian FALKENBACH
Asian Journal of Andrology 2025;27(5):581-585
Androgen deprivation therapy (ADT) can negatively affect sexual function, and only a minority of patients report sexual activity. We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT. The PubMed database was searched for studies published over the past 20 years. We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT. The primary outcome measure was the sexual function. Studies assessed sexual function using quality of life patient-reported outcome measures, which included sexual potency/activity evaluation. Information from 2947 patients was analyzed in this review. The median age of patients was 70 years. At baseline, a median of 49.9% (95% confidence interval [CI]: 49.1%-50.7%) of the patients reported being sexually active. At 6 months, 12 months, and 2 years or later of ADT treatment, a median of 10.3% (95% CI: 10.2%-10.5%), 8.9% (95% CI: 8.6%-9.2%), and 8.3% (95% CI: 8.2%-8.5%) of the patients reported being sexually active, respectively. Considering that half of the patients were sexually active at baseline, it seems probable that more than 10% of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT. In conclusion, despite the common belief that ADT eliminates sexual activity, this analysis found that approximately 1 in 10 men are sexually active when on ADT, and this proportion is likely increased in men who are sexually active before starting ADT. Attention to sexual activity should not be dismissed in men on ADT.
Humans
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Male
;
Prostatic Neoplasms/drug therapy*
;
Androgen Antagonists/therapeutic use*
;
Sexual Behavior/drug effects*
;
Quality of Life
;
Aged
7.Sexual function recovery following open and robotic radical prostatectomy: results of an academic penile rehabilitation program.
Michele Di NAUTA ; Ugo Giovanni FALAGARIO ; Anna RICAPITO ; Matteo RUBINO ; Pasquale ANNESE ; Gian Maria BUSETTO ; Luigi CORMIO ; Giuseppe CARRIERI ; Carlo BETTOCCHI
Asian Journal of Andrology 2025;27(6):680-685
Despite surgical advancements, erectile dysfunction (ED) is a common consequence of radical prostatectomy (RP). This study aimed to evaluate the impact of early penile rehabilitation within a dedicated penile rehabilitation program on assisted and unassisted erectile function (EF) recovery. All patients who underwent RP and at least 1 year follow-up at penile rehabilitation program in the Department of Urology, OORR Policlinico Riuniti (Foggia, Italy) were included. Treatment involved phosphodiesterase type 5 inhibitors (PDE5Is; tadalafil 20 mg, 1 tablet every other day), intracavernous injections (Caverject 5 µg, 1 vial per week), and daily use of vacuum erection devices (VEDs). Primary end point was EF recovery defined as International Index of Erectile Function-5 (IIEF-5) ≥21 with or without rehabilitation aids. IIEF-5 and prescribed treatments were prospectively collected at 3 months, 6 months, 9 months, 12 months, and 24 months. Among 570 eligible patients, 397 (69.6%) underwent rehabilitation. Patients who undergoing andro-rehabilitation were younger (65 months vs 70 months; P < 0.0001), had lower prostate-specific antigen (PSA) levels (5.9 ng ml -1 vs 6.2 ng ml -1 ; P = 0.04), and lower grade tumors ( P = 0.001) compared to the patients who did not undergo sexual rehabilitation after radical prostatectomy. Two-year EF recovery rates in patients undergoing andro-rehabilitation ranged from 75% (preoperative IIEF-5 >16) to 45% (preoperative IIEF-5 <16) with rehabilitation aids. Combination treatments (PDE5I+VEDs with or without intracavernous injections) showed the highest rates of EF recovery (up to 80% at 2 years). EF recovery without rehabilitation aids was significantly higher for patients with IIEF-5 >21 (IIEF-5 >21 [36%] vs IIEF-5 of 17-21 [18%]; P = 0.01). Subanalysis indicated a moderate benefit of rehabilitation in patients with preoperative IIEF-5 <16 who underwent bilateral nerve-sparing RP. Participation in intensive penile rehabilitation programs improves EF recovery in patients undergoing RP. Preserving the neurovascular bundles may be beneficial for patients with preoperative ED.
Humans
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Male
;
Prostatectomy/rehabilitation*
;
Middle Aged
;
Erectile Dysfunction/drug therapy*
;
Aged
;
Recovery of Function
;
Robotic Surgical Procedures/adverse effects*
;
Phosphodiesterase 5 Inhibitors/therapeutic use*
;
Penile Erection
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Tadalafil/therapeutic use*
;
Prostatic Neoplasms/surgery*
;
Treatment Outcome
8.Advances in cancer stem cell markers and their targeting aptamers.
Shangyang PAN ; Wenjing ZHANG ; Xiaoyang CHEN ; Yan LIU ; Ruolan CHEN ; Shuyue MENG ; Zhao YANG
Chinese Journal of Biotechnology 2025;41(8):3008-3020
Cancer ranks as the second leading cause of death globally and has surpassed cardiovascular diseases to become the primary cause of mortality in developed countries. Cancer stem cells (CSCs), which play crucial roles in cancer recurrence, metastasis, and drug resistance, have attracted significant attention in targeted therapeutic strategies. Aptamers, with unique three-dimensional structures capable of specifically recognizing the surface markers of CSCs, show promising potential in targeted drug delivery systems. Compared with conventional antibodies, aptamers are praised for small molecular weights, low production costs, and easy chemical modification. This review systematically summarizes recent advances in aptamer research targeting the surface markers of CSCs, with particular emphasis on aptamer-drug conjugate systems targeting the markers including EpCAM, CD133, CD44, and ABCG2. Both in vitro cellular studies and in vivo animal models have demonstrated the definite anti-cancer efficacy of aptamer-based drug delivery systems, which are of great significance to develop novel therapeutic strategies and improving the therapeutic effects of CSC-targeted treatment. Thus, aptamer-based drug delivery system has broad application prospects in the field of precise cancer treatment.
Humans
;
Neoplastic Stem Cells/metabolism*
;
Aptamers, Nucleotide/therapeutic use*
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Drug Delivery Systems/methods*
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Neoplasms/drug therapy*
;
Biomarkers, Tumor/metabolism*
;
Animals
;
Epithelial Cell Adhesion Molecule
;
AC133 Antigen
;
Hyaluronan Receptors
9.pLM4ACP: a model for predicting anticancer peptides based on machine learning and protein language models.
Yitong LIU ; Wenxin CHEN ; Juanjuan LI ; Xue CHI ; Xiang MA ; Yanqiong TANG ; Hong LI
Chinese Journal of Biotechnology 2025;41(8):3252-3261
Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning
;
Antineoplastic Agents/chemistry*
;
Humans
;
Peptides/chemistry*
;
Support Vector Machine
;
Algorithms
;
Computational Biology/methods*
;
Neoplasms/drug therapy*
10.Research Progress in Immune Checkpoint Inhibitors for Relapsed and Refractory Malignant Gonadal Germ Cell Tumors.
Acta Academiae Medicinae Sinicae 2025;47(1):131-136
Germ cell tumors typically occur in the gonadal regions,characterized by high malignancy and rapid progression.Due to their high sensitivity to chemotherapy,the cure rate is generally high.However,a portion of patients still succumb to chemotherapy resistance and disease progression.The use of immune checkpoint inhibitors has significantly improved the prognosis for various solid tumors,while the immune mechanisms and efficacy of immunotherapy in germ cell tumors remain understudied.Whether relapsed and refractory germ cell tumors can benefit from immune checkpoint inhibitors remains to be investigated.In this review,we summarize the immune-related mechanisms,case reports,and clinical trials of immunotherapy in germ cell tumors to assess the effectiveness of this therapy,providing a reference for future basic research and clinical practice.
Humans
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Neoplasms, Germ Cell and Embryonal/therapy*
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Immune Checkpoint Inhibitors/therapeutic use*
;
Immunotherapy
;
Testicular Neoplasms/drug therapy*
;
Neoplasm Recurrence, Local
;
Drug Resistance, Neoplasm

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