Platinum-based complexes, particularly divalent platinum [platinum(Ⅱ), Pt(Ⅱ)] compounds, have become classic chemotherapy agents for the treatment of malignant tumors. However, their widespread clinical use is limited due to issues such as insufficient stability, the induction of acquired resistance and strong cytotoxicity. Although antibodies that interfere with the interaction between programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1), in combination with platinum-based compounds, have shown significant clinical progress in cancer treatment, their high efficacy is often accompanied by substantial toxicity and immune-related side effects, which limit their long-term use. In contrast, platinum(Ⅳ) [Pt(Ⅳ)] complexes, with their unique octahedral geometry, have demonstrated promising anticancer potential. By modifying the axial ligands, Pt(Ⅳ)-based complexes not only show higher inertness and improved tumor selectivity, but also enable the targeted release of active ligands in the tumor microenvironment. The mechanism allows Pt(Ⅳ)-based complexes to overcome drug resistance, reduce toxicity and enhance immune system activation, making them a research hotspot in the current cancer field. More importantly, Pt(Ⅳ)-based complexes can exert anticancer effects through multiple pathways including causing DNA damage to trigger apoptosis, autophagy and ferroptosis in tumor cells. This multifaceted action mechanism not only enhances antitumor efficacy but also significantly reduces side effects associated with traditional platinum-based compounds. This review summarizes whole anticancer mechanisms of platinum-based complexes, particularly Pt(Ⅳ) complexes in chemo-immunetherapy combination therapies, discussing their potential in cancer treatment and providing theoretical support for the development of efficient, low-toxicity and highly selective Pt(Ⅳ)-based complexes.

Acute kidney injury (AKI) is a prevalent clinical syndrome characterized by a rapid deterioration in renal function. Naringin, a flavonoid abundant in the Rutaceae family, has been reported to provide protective effects against kidney injury. However, the mechanisms responsible for these effects remain inadequately elucidated. In the present study, the AKI mouse model was established in vivo through a single intraperitoneal injection of 20 mg·kg^-1 of cisplatin, and human kidney-2 (HK-2) cell injury was induced by cisplatin in vitro. Blood urea nitrogen (BUN) and creatinine (CRE) levels were measured using an ELISA kit. Hematoxylin and eosin (H&E) staining, along with periodic acid-Schiff (PAS) staining, were employed to evaluate changes in renal histopathology. Serum concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the mice were assessed using ELISA, and the levels of these cytokines were further analyzed. Morphological alterations in HK-2 cells were examined microscopically. The levels of reactive oxygen species (ROS) in HK-2 cells were quantified using an ELISA kit. The protein expression levels of p-MAPK/MAPK, p-JNK/JNK, p-ERK/ERK, p-NF-κB/NF-κB, p-IκBα/IκBα, IL-6, and TNF-α in renal tissue and HK-2 cells were evaluated through Western blot. The results showed that the serum BUN, Cre, IL-6, and TNF-α levels in the model group mice increased and the renal tissue structure was damaged when compared to the control group, whereas naringin could significantly ameliorate the above pathological changes. Moreover, naringin significantly reduced cisplatin-induced ROS production in HK-2 cells. Western blot results confirmed that naringin notably attenuated the expression of p-MAPK, p-JNK, p-ERK, p-NF-κB, p-IκBα, IL-6, and TNF-α proteins in vitro and in vivo. In conclusion, naringin may ameliorate cisplatin-induced AKI by inhibiting the activation of the MAPK/NF-κB pathway and reducing the production of ROS. All animal experiments were approved by the Institutional Animal Care and Use Committee of Hubei University of Chinese Medicine (approval No: HUCMS202204001).

Wound healing caused by skin trauma and chronic diseases is often complicated and difficult due to infection. In such cases, the wound healing process is not only a long and continuous one, but also prone to scar repair. Conventional dressings and antibiotic treatments suffer from issues such as low drug delivery efficiency and systemic toxicity. In recent years, microneedle technology has been widely used to reduce infection and promote wound healing. Microneedles can not only penetrate the skin stratum corneum and biofilm to enhance drug delivery efficiency and reduce drug side effects, but also can be combined with a variety of materials to achieve multiple treatments and monitoring of wounds. This article will discuss the healing mechanism of infected wounds, the classification of microneedles, and their applications in the treatment of infected wounds.

Resiquimod (R848) belongs to the class of weak base organic compounds that are derivatives of imidazole quinoline and is a potent agonist of Toll-like receptor (TLR) 7/8. R848 can be considered an effective immune adjuvant as it has the ability to activate different immune cells and regulate innate and adaptive immunity. A number of researches done recently have reported R848 potent anti-tumor capacity, especially when combined with other cytotoxic therapies. Nonetheless, some hurdles remain with the clinical use of R848 such as its limited ability to reach the tumor and likelihood of inflammation and autoimmune responses which might result from repeated delivery of high dosages of the drug. Nanoscale drug delivery systems may overcome some of these challenges. Various nanoformulations, including liposomes, polymeric nanoparticles, biocarriers, inclusion compound, metal-organic frameworks and inorganic nanoparticles, as well as several R848 prodrugs or derivatives-baesd nanoparticles, have been incorporated into present R848 delivery platforms. This article reviews the physicochemical properties, immune regulatory mechanisms and nano drug delivery systems of R848, in order to provide reference and support for anti-tumor research and new drug development.

The study investigates the therapeutic effects and mechanisms of Buyang Huanwu Decoction (BHD) in treating ischemic stroke (IS). Using a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model, we evaluated the neuroprotective effects of BHD, demonstrating significant improvements in neurological function scores, prolonged rotarod retention time, and reductions in both infarct volume and brain water content. An unsupervised clustering algorithm was employed to identify active components of BHD by clustering them with FDA-approved drugs for ischemic stroke treatment. Combined with network pharmacology analysis, the mechanisms of these active components were predicted to be associated with anti-inflammatory pathways. Further validation using a lipopolysaccharide (LPS)-induced BV-2 cell model demonstrated the anti-inflammatory efficacy of seven key active components, with their effects on anti-inflammatory activity and cell viability assessed via the Griess and MTT assays. Additionally, the content of these active components in BHD was quantified using liquid chromatography-mass spectrometry (LC-MS). In conclusion, this study elucidates the critical active components of BHD and their potential pharmacological mechanisms, providing valuable insights for the modernization of traditional Chinese medicine and its application in ischemic stroke therapy. All animal experiments were approved by the Animal and Medical Ethics Committee of Northeastern University (approval No.: NEU-EC-2023A052S).

Prenylated aromatic natural products (PANPs) are widely distributed in nature. PANPs exhibit a great structural diversity due to their various core scaffolds (coumarin, lignan, benzoic acid/benzyl alcohol, flavonoid, xanthone, anthraquinone, and aromatic alkaloid, etc.) and the distinct types and substitution sites of isoprenoid moieties which may possess either linear or cyclic structures. The structural diversity of PANPs endow them with various bioactivities including anti-bacterial, anti-oxidation, anti-cancer, anti-inflammatory and analgesic effects, which makes them a group of highly promising molecules for drug development. Notably, isoprenoid moieties are often the indispensable pharmacophores in these active PANPs. Aromatic prenyltransferases (aPTs) are responsible for prenylation in the biosynthesis of PANPs. aPTs can be divided into three classes according to their evolutionary relationships and structural features, i.e. membrane-bound aPTs (UbiA type), soluble aPTs with a PT barrel structure (ABBA type and DMATS type) and terpene synthase-like aPTs. Herein, we summarize 94 aPTs belonging to the different classes which were characterized in the past ten years, in particular introduce their substrate selectivity/tolerance, regioselectivity, evolutionary relationships and structural features. This would provide cues for discovery and engineering of new aPTs, and modification and bio-production of active PANPs.

Usenamine A (UA) is a dibenzofuran compound isolated from Usnea longissima Arch. Previous studies have demonstrated that UA exhibited significant in vitro and in vivo anti-hepatocellular carcinoma activity, inducing both apoptosis and autophagy in human hepatocellular carcinoma cells. This study aims to further elucidate the molecular mechanism underlying its anti-hepatocellular carcinoma effect. Based on data obtained from gene chip assay, real-time quantitative PCR, and Western blot analysis, we found that UA effectively inhibited the expression of polo-like kinase 1 (PLK1) in human hepatocellular carcinoma HepG2 and SK-HEP-1 cells. Furthermore, the administration of BI 6727, a PLK1 inhibitor, significantly diminished the inhibitory effect of UA on the viability of human hepatocellular carcinoma cells. Additionally, the knockdown of PLK1 expression via RNA interference markedly inhibited the proliferation of human hepatocellular carcinoma cells, and the inhibitory effect of UA on cell viability was attenuated upon PLK1 knockdown. The knockdown of PLK1 expression significantly upregulated the apoptosis rate of human hepatocellular carcinoma cells and notably diminished the apoptosis-inducing effect of UA on these cells. Additionally, the inhibition of autophagy using the autophagy inhibitor 3-MA reduced the proliferation-inhibitory effect of UA on human hepatocellular carcinoma cells. Utilizing the PLK1 inhibitor BI 6727 or RNA interference, we further demonstrated that PLK1 negatively regulated autophagy in human hepatocellular carcinoma cells. Consequently, the inhibition of PLK1 attenuated the autophagy induction by UA on these cells. Thus, PLK1 plays a crucial role in the inhibition of human hepatocellular carcinoma cell proliferation and the induction of apoptosis by UA. Moreover, UA activates autophagy through the inhibition of PLK1, which subsequently exerts an inhibitory effect on the growth of human hepatocellular carcinoma cells.

The chemical constituents of the fruits of Forsythia suspensa (Thunb.) Vahl were investigated by using chromatographic techniques (silica gel, MCI, and sephadex LH-20 gel column chromatography, etc). Fourteen compounds were isolated from the 95% ethanol extract of F. suspensa, and their structures were identified by HR-ESI-MS, NMR, and calculated electronic circular dichroism (ECD) methods. The compounds included labdane diterpenes (1-6), clerodane diterpene (7), norlabdane diterpene (8), norclerodane diterpene (9), oleanane triterpenoid (10), ursane triterpenoids (11, 12), lupane triterpenoids (13, 14). Among them, compound 1 was a new compound and compounds 3-9, 11, and 12 were obtained from this plant for the first time. The inhibitory effect of these compounds on lipopolysaccharide-induced nitric oxide production in mouse macrophage RAW 264.7 cells also was evaluated. Unfortunately, none of these compounds exhibited significant inhibitory activity.

Plant-derived extracellular vesicles (PDEVs) are lipid bilayer-structured nanovesicles secreted by plant cells, recognized as excellent drug carriers due to their high stability, safety, and modifiability. As an emerging drug delivery system, PDEVs are gaining increasing attention. This review systematically summarizes the latest research progress on the preparation, characterization, engineering transformation, drug loading methods, and the applications and advantages of PDEVs as drug carriers. Finally, the future development directions of PDEVs in drug delivery are discussed.

A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg^-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg^-1. This method has been applied to the determination of real samples.