Five sesquiterpenoids were isolated from a 50% acetone extract of Cornus officinalis leaves, a traditional non-medicinal part of Cornus officinalis, using modern column chromatographic techniques such as macroporous adsorbent resins colum, silica gel colum, chromatography gel colum and semi-preparative liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as cornurtone A (1), cornucadinoside B (2), lacinilene C (3), 3, 12-dihydroxycadalene (4), cornucadinoside C (5). Compound 1 was new compound and compounds 2-5 were first isolated from leaves of Cornus officinalis. Compounds 2 and 3 had potential neuroprotective activities.

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.

Human influenza is mainly caused by influenza A virus and influenza B virus, and it is one of the most serious infectious diseases that pose a serious threat to human health. Currently, there are few marketed drugs for influenza viruses, and the existing drugs are faced with problems such as drug resistance. The development and research of combinations of anti-influenza drugs have gradually attracted people's attention. At present, certain progress has been made in aspects such as the discovery of anti-influenza drug combinations and the evaluation of drug effects. Discovering effective combination drugs is an ideal method for repurposing old drugs. That can be used to improve therapeutic effects and delay or reduce the occurrence of drug resistance. Herein, this article introduces the evaluation methods, models of combinations of anti-influenza drugs, as well as available data resources and tools, and summarizes the latest progress in the current research on combinations of anti-influenza drugs, with the aim of providing a reference for the research and development of the combined application of anti-influenza virus drugs.

There are abundant resources of traditional Chinese medicine in China, and it is found that the effective components of traditional Chinese medicine contain functional groups that are easy to coordinate with metal ions, such as amino, carboxyl and hydroxyl, which can complex with transition metal ions to derive new compounds. These traditional Chinese medicine metal complexes often exhibit unique properties and functions compared with their corresponding monomers, providing a new path for new drug development. Based on the formation principle of metal complexes with traditional Chinese medicine and the common coordination metal ions, in this review, the effective components in traditional Chinese medicine are roughly divided into anthraquinone, alkaloid, flavone, coumarin, amino acids and polysaccharide compounds, so as to provide new ideas for the discovery of new traditional Chinese medicine, and provide scientific basis for the modernization and internationalization of traditional Chinese medicine.

Exosomes are small vesicles secreted by cells that contain important bioactive molecules such as nucleic acids and proteins. Increasing research indicates that exosomes play a unique and crucial role as signal molecule carriers in various diseases, and they exhibit great potential in disease diagnosis and treatment. Recent studies have shown that exosomes play an important role in immune regulation. The NOD (nucleotide binding oligomerization domain)-like receptors protein 3 (NLRP3), an essential component of the innate immune system, plays a key role in the occurrence and development of various diseases including autoimmune diseases, metabolic diseases, and neurodegenerative diseases. Its activation and regulatory mechanisms are complex and diverse. However, the regulatory mechanisms associated with exosomes and NLRP3 inflammasome have not yet been fully elucidated. This article reviews the regulatory effects of exosomes from different sources on the NLRP3 inflammasome and summarizes the therapeutic potential of exosomes in diseases associated with the NLRP3 inflammasome, aiming to provide new ideas for the prevention and treatment of diseases related to the NLRP3 inflammasome.

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.

This study investigated the material basis of Huoluoxiaolingdan in treating diabetic peripheral neuropathy (DPN) through ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and network pharmacology. UPLC-Q-TOF-MS/MS combined with PeakView^TM 1.2 software and Molecule Profiler^TM software were used to analyze the the chemical components of Huoluoxiaolingdan and blood-absorbed ingredients in normal rats and rats with DPN induced by high fat diet combined with low dose streptozotocin injection. Swiss Target Prediction database, GeneCards and other databases were used to search the corresponding targets of active ingredients and disease targets. The intersection targets were obtained using Venny 2.1 platform, which were then imported into the STRING platform and Cytoscape 3.10.1 software to construct the protein-protein interaction network and the "component-target" network relationship diagram, and the core components and core targets were analyzed. GO and KEGG pathway enrichment analysis of key targets were performed. All experiments were approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202310A023). A total of 83 chemical components were identified, including 52 terpenoids such as tanshinone Ⅱ_A, 11 phthalides such as Z-ligustilide, 15 organic acids such as ferulic acid, 4 coumarins and 1 phenol. Additionally, 15 prototype components and 29 metabolites were identified in normal rats' plasma, and 17 prototype components and 32 metabolites were identified in DPN rats' plasma. Network pharmacology results show that 5 core components such as 3-acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid may act through 27 core targets such as TNF and IL6 to regulate AGE-RAGE and PI3K/Akt and other signaling pathways so as to play a therapeutic role in treatment of DPN. The study efficiently analyzed the constituents in vitro and blood-absorbed ingredients of Huoluoxiaolingdan and the cracking regularity of the main compounds, and the core components of its treatment of DPN were analyzed in combination with network pharmacology, which can provide reference for further research of the pharmacodynamic substantial basis and mechanism of Huoluoxiaolingdan in the treatment of DPN.

Cocktail probe drug method was used to evaluate the effect of cold treatment drugs such as Gegen Decoction on cytochrome P450 (CYP450) enzyme activity in rat liver. The in vitro incubation system of rat liver microsomes was optimized. Based on LC tandem mass spectrometry (LC-MS/MS), an analytical method for simultaneous determination of the content of metabolites of each subenzyme probe in rat liver microsome CYP450 enzyme was established. Cocktail probe drug method was used to characterize the effects of Gegen Decoction, a classical prescription for the treatment of wind-cold cold, and acetaminophen, chlorpheniramine maleate, anhydrous caffeine and nacotine hydrochloride, which were commonly used in the treatment of cold, on the activity of CYP2D6, CYP2C9, CYP3A4 and other sub-enzymes in rat liver microsomes, so as to provide reference for the safety of clinical drug combination. The results showed that the established analysis method was stable and reliable, which met the requirements of biological sample determination. After optimization, the protein concentration of rat liver microsomes in the incubation system was 3.00 mg·mL^-1, the incubation time was 240 min, and the terminator was acetonitrile. The K_m values of three CYP subenzyme specific probe substrates dextromethorphan, testosterone and tolbutamide were 21.49, 87.33 and 354.7 μmol·L^-1, respectively. The effectiveness of the established incubation system was verified by positive inhibitors. Compared with the blank control group, when the concentration of each Western medicine and the concentration of Gegen Decoction extract were within 100.00 μmol·L^-1 and 3.00 mg·mL^-1, respectively, Gegen Decoction extract, chlorpheniramine maleate and noscapine hydrochloride had inhibitory effects on CYP2C9 and CYP2D6 enzymes in rat liver microsomes; anhydrous caffeine had inhibitory effects on CYP2C9 and CYP3A4 enzymes in rat liver microsomes; no significant inhibitory effect on acetaminophen; the induction effect of narcotine hydrochloride on CYP3A4 enzyme in rat liver microsomes was greater than 40% of the activity of positive inducer, suggesting that there may be a certain risk of drug interaction when combined with narcotine hydrochloride, and attention should be paid to the dose of drug treatment. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulacspf2022137).

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.

Respiratory infections, as common diseases, along with other respiratory system diseases such as asthma, rare diseases including cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer, can be prevented using vaccines. Taking respiratory infections as an example, vaccines are mostly administered via intramuscular injection, inducing the production of serum IgG, thereby neutralizing viral infectivity and alleviating COVID-19 symptoms. However, due to the lack of secretory IgA and IgG in muscle tissues, intramuscular vaccines cannot quickly provide protection to the respiratory tract. To overcome the shortcomings of intramuscular injection, some vaccine candidates for nasal or nebulized inhalation are under development or have been approved. Clinical studies show that inhaled vaccines can induce antibody responses similar to those of intramuscular vaccines at much lower doses. Inhaled vaccines can simultaneously induce humoral, cellular, and mucosal immunity, providing triple protection. With the application of new vaccines (e.g. mRNA vaccines and DNA vaccines) in inhalable formulations for COVID-19, inhaled vaccines have been proven to have broad application prospects in the prevention of lung diseases. Given this background and the known abundance of immune cells in the lungs, increasing research efforts are devoted to developing single-dose inhalable nano dry powder vaccines. This article discusses the roles and advantages of inhaled vaccines in mucosal immunity, their potentials for treating different diseases, and prospects for the future development of inhaled vaccines based on nanotechnology.