Radiopharmaceuticals play a crucial role in nuclear medicine, with the development of radioligands being a key focus in this field. Peptide-based radiopharmaceuticals have shown significant advantages in clinical applications, with the majority of FDA-approved targeting radiopharmaceuticals since 2018 being derived from peptides or peptidomimetics. Bicyclic peptides have emerged as a promising targeting moiety in radioligands, offering improved biophysical properties compared to linear or monocyclic peptide ligands. This article provides an overview of the methods for obtaining bicyclic peptide ligands, as well as highlighting the major clinical and preclinical advancements in bicyclic peptide-based radiopharmaceuticals. The review also discusses the future prospects of bicyclic peptide-based radiopharmaceuticals, offering insights for practitioners in the field of pharmaceutical science and nuclear medicine to keep up with the latest developments in radiopharmaceutical innovation.

Liver fibrosis is a common stage in the progression of chronic liver diseases, yet there is a lack of clinical drugs against liver fibrosis globally. Gynostemma pentaphyllum has the name of "Southern ginseng", commonly used in folk prevention and treatment of a variety of chronic liver disease, there are also reports of its anti-hepatic fibrosis. However, there are fewer relevant scientific studies. In this study, we used LC-MS metabolomics analysis to investigate the effects of Gynostemma pentaphyllum ethanol extract (GPE) on liver fibrosis in carbon tetrachloride (CCl₄)-induced mouse models and its potential mechanisms. All animal experiments were approved by the experimental animal ethics committee of Capital Medical University (DWLLGZR202202204). The results showed that GPE could significantly reduce the inflammatory cell infiltration and collagen accumulation in the liver of model mice, significantly reduce serum alanine transaminase and aspartate transaminase activity and hypoxanthine levels in mice, and could effectively inhibit the gene transcription and protein expression of collagen 1A1 (COL 1A1) and α-smooth muscle actin (α-SMA). Non-targeted metabolomics analysis of the liver showed that GPE mainly affected 47 differential metabolites; KEGG pathway enrichment analysis indicated that the differential metabolites were mainly enriched in the fructose/mannose metabolism and aromatic amino acid metabolism pathways. The targeted metabolomic assay was further used to validate a total of 13 differential metabolites of D-mannose, mannose 6-phosphate, D-fructose, fructose 2-phosphate, D-sucrose, trehalose, glutamate, phenylalanine, tyrosine, L-2-amino-3-oxobutyric acid, lactate, 2-hydroxybutyrate, and taurine, which may be important metabolites related to GPE's anti-fibrotic effects. This confirms that GPE's anti-liver fibrosis effects may be closely related to the regulation of the fructose/mannose metabolism pathway and the aromatic amino acid metabolism pathway.

Severe alcoholic hepatitis (SAH) represents the most extreme form of alcoholic liver disease (ALD), accompanied by an extremely high mortality rate. Currently, there is a dearth of appropriate animal models for related research. The objective of this study is to establish a mouse model of SAH, thereby providing a preclinical animal model for subsequent research on SAH. This study is based on the NIAAA (National Institute on Alcohol Abuse and Alcoholism) model and constructs a mouse model by combining bacterial endotoxins. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-102). The model emulates the pathological processes of clinical SAH in terms of mouse mortality, liver tissue damage, and inflammatory markers, thereby establishing the model. Ultimately, it is ascertained that the optimal conditions for SAH mouse modeling based on the NIAAA model are the last intragastric administration of alcohol at a concentration of 7.5 g·kg^-1 in combination with intraperitoneal injection of lipopolysaccharide at a dose of 5 mg·kg^-1 for a period of 12 h. Under these conditions, the mouse model effectively simulates the high mortality and liver dysfunction seen in clinical SAH, with pathological staining results closely mirroring clinical findings. Additionally, it demonstrates a significant infiltration of neutrophils in the liver, indicative of an excessive inflammatory response. This model provides an ideal platform for preclinical research on SAH.

This study aimed to clarify the mechanism and active components of Buyang Huanwu Decoction (BYHWD) in alleviating cerebral ischemia reperfusion injury (CIRI) by inhibiting pyroptosis. The key components and targets of BYHWD for CIRI were identified via network pharmacological analysis, followed by molecular docking performed with Autodock and Pymol software. The effects of BYHWD and its active components were validated in vivo and in vitro. A middle cerebral artery occlusion (MCAO) model was established in mouse to assess neural function alterations in mice under various conditions. Concurrently, an oxygen-glucose deprivation/reperfusion (OGD/R) model was developed utilizing mouse brain tissue astrocytes in vitro. Molecular biology experiments were used to verify the predicted key targets. We have determined that the principal components of BYHWD are baicalein and β-sitosterol. By analyzing genes associated with CIRI pathology alongside those linked to pyroptosis, 20 intersecting genes were identified. In conjunction with molecular docking binding energy assessment, TP53 and TNF emerged as pivotal core targets for subsequent validation. Molecular biology experiments confirmed that BYHWD effectively alleviates injury while reducing the expression level of P53. These findings indicate that the primary bioactive constituents of BYHWD were baicalein and β-sitosterol. In addition, BYHWD may inhibit pyroptosis via TNF and TP53 in protecting CIRI. The experiment has been approved by the Experimental Animal Welfare Ethics Committee of Zhejiang Academy of Traditional Chinese Medicine, approval number (KTSC2020037, KTSC2023030).

Tumor immunotherapy represented by blocking programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) has gained better therapeutic effect in lung cancer treatment, and the development of small molecule drugs to block PD-1/PD-L1 provides a new strategy for lung cancer immunotherapy. In this study, we applied an in vitro cell model to investigate the regulation of PD-L1 expression and the mechanism of action of baicalin on A549 lung cancer cells. The effects of baicalin on the viability of A549 cells were detected by CCK8 assay; the expression of PD-L1 protein in A549 cells was detected by Western blot; the mechanism of baicalin cytotoxicity and its correlation with PD-L1 protein expression were investigated by using small-molecule inhibitors of apoptosis and autophagy; the formation of autophagic vesicles in A549 cells treated with baicalin was observed under transmission electron microscope. And the alterations of acid autophagic vesicles and autophagic lysosomes were observed under fluorescence microscope. The results of CCK8 experiments showed that baicalin (12.5-400 μmol·L^-1) inhibited the proliferation of A549 cells in a dose-dependent manner; at the same time, the elevation of PD-L1 protein expression after interferon-γ (IFN-γ) interference could be reduced with the increase of baicalin concentration; on the other hand, treatment with autophagy inhibitors, wortmannin, and chloroquine, could call back the baicalin-induced cytotoxicity, transmission electron microscopy and fluorescence microscopy showed that the number of autophagic vesicles increased after baicalin treatment of A549 cells, and Western blot results showed that baicalin promoted the expression of autophagy-related proteins LC3-Ⅱ/Ⅰ and beclin-1; the number of baicalin-induced acidic autophagic vesicles in A549 cells was attenuated after the intervention of wortmannin, and at the same time the LC3-Ⅱ/Ⅰ expression was inhibited and the inhibitory effect on PD-L1 was regulated. The above results suggest that baicalin may exert antitumor effects by activating the autophagy protein LC3 in A549 cells to reduce the expression of PD-L1. This study lays the foundation for baicalin to have the ability to be developed as a small molecule blocker of the PD-1/PD-L1 signaling pathway.

Artificial intelligence (AI) technology is increasingly applied across various fields, particularly in handling and analyzing large volumes of data, providing breakthroughs for numerous scientific studies. In Chinese medicine research, AI demonstrates significant advantages by enhancing the systematic, efficient, and accurate nature of studies through its exceptional learning and data processing capabilities. As a discipline with a long-standing history and rich theoretical framework, Chinese medicine research requires the integration of complex information, for which AI provides crucial support. AI technologies, especially machine learning and deep learning, can decipher complex biological and chemical data, advancing new discoveries in Chinese medicine pharmacology. Researchers can systematically analyze the multi-target mechanisms of Chinese medicine components and optimize formulation efficacy through these technologies. The combination of AI with multi-omics data and its application in cell phenotype analysis aids in accurately identifying drug targets and exploring new mechanisms. Additionally, AI-integrated network pharmacology combines experimental, computational, and clinical data to analyze multi-target drug mechanisms, enhancing the efficacy of TCM formule. AI accelerates the target identification of active compounds as well as dissecting the pharmacological effects. The development of large language models also plays a crucial role in constructing Chinese medicine knowledge graphs and literature analysis, extracting valuable information from extensive literature using natural language processing to build a systematic knowledge structure. The introduction of AI technology has propelled the modernization of Chinese medicine research and has a pivotal role in the development of internationalization and precision medicine. AI not only enhances the overall level of Chinese medicine research but also provides a solid foundation for interdisciplinary collaboration and innovation. With the continuous advancement of AI technology, Chinese medicine is anticipated to have a greater influence and role globally. This process is not only a significant marker of the modernization of Chinese medicine but also a reflection of the integration of science and traditional wisdom, which will undoubtedly drive progress and development in the entire medical field.

Twenty compounds were isolated from the twigs and leaves of the 95% ethanol extract of Miliusa tenuistipitata W. T. Wang by various chromatographic techniques including silica gel column chromatography, sephadex LH-20 and preparative HPLC. Their structures were determined by analysis of spectral data as tenuistone L (1), tenuistone K (2), sakuranetin (3), pachypodol (4), retusin (5), penduletin (6), casticine (7), 3, 7-dimetoxi-5, 3′, 4′-tri-hidroxiflavona (8), eupatin (9), (+)-miliusol (10), miliusane XIX (11), miliusane XVIII (12), miliusolide (13), 19, 20-dihydromiliusolide (14), debilisone C (15), goniothalamusin (16), 2, 10-dihydroxy-3, 9-dimethoxy-8-oxo-protoberberine (17), consanguine B (18), 6β-hydroxystigmasta-4, 22-dien-3-one (19) and 6β-hydroxystigmast-4-en-3-one (20), respectively. Among them, compounds 1 and 2 are new compounds, compounds 6, 9, 18 and 20 are isolated from Annonaceae plants for the first time and compounds 5, 7, 17 and 19 are isolated from the genus Miliusa for the first time. Human triple negative breast cancer cells (MDA-MB-231 and BT-549) were used to evaluate the antitumor activity of these isolates by MTT assay. Compounds 10 and 11 showed significant anti-proliferation activity against the test cells with half inhibition concentration (IC₅₀) of 0.98-4.85 μmol·L^-1.

Non-small cell lung cancer (NSCLC) is the primary pathological type of lung cancer. Osimertinib, as a third-generation EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) targeted drug, effectively prolong the progression-free survival of patients with EGFR-mutated NSCLC. However, drug resistance limits the efficacy of osimertinib. Traditional Chinese medicine can effectively delay the resistance to EGFR-TKIs. In this study, Cucurbitacin B (CuB) was investigated to analyze its pharmacological effects in osimertinib-resistant NSCLC cells through cell viability, migration, and invasion experiments. Public databases were used to screen potential targets of CuB in osimertinib-resistant NSCLC cells, and the interactions between CuB and potential targets were verified through molecular docking, cellular thermal shift assay (CETSA), and microscale thermophoresis (MST). Western blot was used to detect the effects of CuB on downstream pathways of the targets. The results showed that CuB significantly reduced the proliferation activity of osimertinib-resistant NSCLC cells and inhibited the migration and invasion abilities of tumor cells. Mechanistically, CuB inhibited the expression of ERK and AKT molecules by binding to the tyrosine kinase receptor AXL. In summary, CuB exhibits resistance to osimertinib-resistant NSCLC by inhibiting the migration and invasion of resistant cells through regulating the abnormal activation of the AXL-ERK/AKT axis. This study provides a basis for the pre-clinical in vitro efficacy of CuB in the treatment of osimertinib targeted resistance in NSCLC and theoretical support for the development of clinical drug combinations.

This study mainly explored the anti-tumor effects of programmed death ligand 1/ transforming growth factor-β (PD-L1/TGF-β) bispecific antibody drugs in the huHSC-NCG mouse brain orthotopic transplantation model of human glioma cell U251-luciferase (all animal experiments in this study were approved by the Experimental Animal Ethics Committee of GemPharmatech, and the ethics review number is GPTAP20230706-3). The antibody-antigen binding activity of the PD-L1/TGF-β bispecific antibody drugs to PD-L1 target on U251 cells was detected by flow cytometry in vitro. The antitumor activity of PD-L1/TGF-β bispecific antibody drugs was evaluated using a brain glioma in orthotopic implantation model with humanized immune system. Live animal imaging and brain tissue (including tumor tissue) weight results showed that the PD-L1/TGF-β dual antibody drug had an inhibitory effect on the growth of glioma in situ. The results of drug content (ELISA assay) and drug distribution (immunohistochemistry assay) in brain tissue showed that PD-L1/TGF-β dual antibody could enter the brain glioma and play the function of immune checkpoint, thus playing an inhibitory role in brain glioma. Immunofluorescence staining of mouse brain tissue showed that the drug activated the immune system and had synergistic anti-tumor effect with the immune system. These results showed that the PD-L1/TGF-β bispecific antibody drugs have broken through the blood-tumor barrier in orthotopic implantation model of mouse brain glioma and demonstrated a strong anti-tumor effect. In conclusion, the inhibitory effects of PD-L1/TGF-β bispecific antibody drugs on human brain glioma provides a new strategy for the treatment of human brain glioma.

Autophagy is an important physiological process that can degrade cellular components and maintain cellular homeostasis. In the process of cancer development, autophagy plays a dual role in promoting or inhibiting autophagy, and targeting autophagy is considered to be an important means of cancer treatment. According to Chinese medicine theory, autophagy has the function of regulating the balance of Yin and Yang, and the balance of good and evil in the organism, and based on the theory of "supporting the positive and dispelling the evil", the use of active ingredients of traditional Chinese medicine (TCM) to target autophagy has been proven to be effective in the treatment of cancer. In addition, autophagic cell death, as a type Ⅱ programmed cell death, is often accompanied by autophagic features, and the regulation of autophagic cell death is an important way for autophagy to achieve anti-tumor effects. In recent years, more and more studies have found that the active ingredients of TCM have good effects in cancer treatment, among which, targeting autophagic cell death is an important way for TCM active ingredients to achieve anti-tumor effects. This paper outlines the understanding of cancer and autophagy in Chinese medicine theory, and summarizes the current Chinese medicine small molecule compounds targeting autophagic cell death and their mechanisms of action based on the classification of natural medicines. Finally, the development of Chinese medicine-derived compounds targeting autophagic cell death for the treatment of diseases is summarized and prospected, which hopefully can provide clues for subsequent exploration and research.