Synthetic cannabinoid N-(1-carbamoyl-2, 2-dimethylpropyl)-1-butylazole-3-formamide (ADB-BUTINACA), as a new psychoactive substance, shows strong stimulant and hallucinogenic effects. It can cause cardiovascular, renal and gastrointestinal diseases, and in severe cases, it can lead to death. However, there are few reports on toxicology studies of the ADB-BUTINACA metabolic pathway and its long-term effects on the organism and the molecular mechanisms behind it. In this study, the metabolic profile of rat serum after low, medium and high doses of ADB-BUTINACA (0.1, 1, and 5 mg·kg^-1) intervention were analyzed using UHPLC coupled with a Q-Orbitrap-MS (UHPLC-Q-Orbitrap-HRMS). The results showed that the intervention of ADB-BUTINACA could cause significant changes of 50 metabolites such as L-glutamate and 3-hydroxybutyrate, and nine metabolic pathways including alanine, aspartate and glutamate metabolism, retinol metabolism, and TCA cycle were disturbed. These findings provide a novel experimental and theoretical framework for further investigation of the toxicological mechanisms underlying ADB-BUTINACA-induced dysregulation of lipid and energy metabolism. Furthermore, they offer valuable insights that could facilitate the diagnosis and prevention of ADB-BUTINACA toxicity, thereby underscoring their significant implications for public health. The study was conducted in adherence to both the Declaration of Helsinki and the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals, and received approval from the animal experimental center at the Zhejiang Chinese Medical University (Ethical number: 20220718-11).

Conjugated estrogens (CE) are widely used in menopausal hormone therapy (MHT) for the relief of menopause-related symptoms (e.g., vasodilatory symptoms, neuropsychiatric symptoms, genitourinary atrophy symptoms, etc.) and the prevention of postmenopausal osteoporosis. This article reviews the characteristics, pharmacological effects, and practical applications of different dosage forms of CE (tablets, creams, and injections) in clinical practice. It has been shown that tablet CE effectively regulates the body's temperature center through systemic treatment, reduces hot flashes and night sweats, promotes bone formation, and increases bone density. Cream CE is used for local treatment to improve the genitourinary syndrome of menopause (GSM). Injectable CE is used for the treatment of abnormal uterine bleeding caused by hormonal imbalance without organ pathology. CE administered intravenously is indicated only for short-term use to rapidly and temporarily increase estrogen levels. Additionally, CE plays an important role in metabolism by improving insulin clearance and sensitivity and potentially protecting the nervous and cardiovascular systems, demonstrating a wide range of therapeutic potential. This paper provides new ideas for the design and development of drug dosage forms by exploring the formulation and application of CE.

To establish the cells stably co-expressing NOD1 receptor and enhanced green fluorescent protein (EGFP)-tagged nuclear factor of activated T cells 2 nuclear factor (NFAT2) (EGFP-NFAT2) in U2OS cell, the NOD1 (NM_006092) pcDNA3.1-3×Flag-hygro recombinant plasmid was transfected into U2OS-EGFP-NFAT2 cells, which were screened by pressure of hygromycin B and then incubated with NOD1 agonist lipopolysaccharides (LPS) for 30 min, and the green fluorescence intensity in the nucleus of the cells was detected by the high content screening assay. There were 46 cell strains expressing NOD1 in U2OS-EGFP-NFAT2 cells by EGFP-NFAT2 nuclear translocation assay. Among these cells, cells No 4 had the highest nuclear translocation function. Therefore, it was selected as the U2OS-EGFP-NFAT2-NOD1 cell for functional validation. The expression levels of NOD1 mRNA and protein in the selected U2OS-EGFP-NFAT2-NOD1 cells and the control cell U2OS-EGFP-NFAT2 were examined by real-time quantitative PCR (RT-qPCR) and Western blot. The results showed that NOD1 mRNA was stably expressed in this stably transfected cell line for 5-20 generations, and NOD1 protein was expressed in U2OS-EGFP-NFAT2-NOD1 stably transfected cell line, whereas no NOD1 protein was expressed in the control cell U2OS-EGFP-NFAT2. U2OS-EGFP-NFAT2-NOD1 cells were treated with histones or LPS for 30 min, and the EGFP-NFAT2 nuclear translocation was detected by the high content screening assay. Histones were found to significantly increase the EGFP-NFAT2 nuclear translocation in U2OS-EGFP-NFAT2-NOD1 stably transfected cells over a range of concentrations. The U2OS-EGFP-NFAT2-NOD1 cells were divided into the solvent control group, NOD1 receptor antagonist nodinitib-1+histone group, and histone group. The drug incubation time was 30 min, and the specificity of the NOD1 cells was verified by observing the EGFP-NFAT2 nuclear translocation through the high content screening assay. Compared with the histones group, the nodinitib-1+histones group significantly decreased EGFP-NFAT2 nuclear translocation in U2OSEGFP-NFAT2-NOD1 cells (P < 0.05). In conclusion, U2OS-EGFP-NFAT2-NOD1 cells stably co-expressing NOD1 and EGFP-NFAT2 are established, which can be used for screening antagonistic compounds targeting NOD1 pathogenic microorganisms with mechanism study.

To investigate the effect and underlying mechanism of action of Yueju volatile oil (YJVO) in the treatment of high altitude sleep disturbance (HASD) mice, gas chromatography-mass spectrometry (GC-MS) was used to identify the components of YJVO, while network pharmacology was applied to predict the mechanism of action. KM mice were selected and randomly assigned to several groups: the control group (control), the model group (model), and the YJVO treatment groups at low (YJVO-L, 200 μL·m^-3), medium (YJVO-M, 400 μL·m^-3), and high (YJVO-H, 800 μL·m^-3) doses, as well as the diazepam group (DZP, 2 mg·kg^-1). Except for the control group, all mice were subjected to a hypobaric oxygen chamber to establish the HASD model. Animal experiments were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics No.: TEMPOR20230088). Co-sleeping and weight-bearing swimming experiments were conducted to assess the sleep-regulating effects of YJVO. Hematoxylin and eosin (H&E) staining was employed to observe damage in hypothalamic and hippocampal brain tissues. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure levels of melatonin (MT), γ-aminobutyric acid (GABA), interleukin-6 (IL-6), interleukin-1beta (IL-1β), 5-hydroxytryptamine (5-HT), orexin-A, and tumor necrosis factor-α (TNF-α) in both plasma and brain tissues. Concurrently, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were detected to evaluate oxidative stress. Western blot was used to determine the expression of key proteins in the NF-κB/NLRP3 pathway, and immunohistochemistry (IHC) was used to detect the expression of 5-hydroxytryptamine 1A receptor (5-HT_1A) in hippocampal and hypothalamic tissues. The GC-MS results revealed that YJVO was identified to contain 68 components. Network pharmacology results indicated that the mechanism of YJVO in treating HASD involves multiple signaling pathways such as AGE-RAGE, TNF, serotonin, and NF-κB. Behavioral experiments indicated that YJVO significantly prolonged the sleep duration, reduced the sleep latency, and bolstered the physical endurance and anti-fatigue capabilities of mice (P < 0.01). H&E staining results showed significant improvement in the pathological damage of the hippocampus and hypothalamus tissues in HASD mice. ELISA results indicated that YJVO increased the concentrations of sleep-inducing neurotransmitters MT and GABA within brain tissues, decreased the levels of wakefulness-inducing neurotransmitters orexin-A and 5-HT in plasma, and attenuated the secretion of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α (P < 0.01). Biochemical results indicated that YJVO could inhibit the production of MDA in the brain tissue of HASD mice and enhance the activity of SOD and GSH-PX (P < 0.01). Western blot results showed that YJVO downregulated the protein expression of phosphorylate nuclear factor-kappa B (p-NF-κB p65)/nuclear factor-kappa B (NF-κB p65), Nod-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (Caspase-1), and IL-1β in the brain tissue of HASD mice (P < 0.01). IHC results demonstrated that YJVO downregulated the protein expression of 5-HT_1A in the hippocampus and hypothalamus tissues of HASD mice (P < 0.01). The study findings indicate that YJVO demonstrates potent therapeutic effects in HASD mice, potentially through the modulation of neurotransmitters and the attenuation of neuroinflammation.

It aimed to research the chemical constituents of Solidago canadensis Lour. A new sucrose derivative was isolated from the the methanol extract of Solidago canadensis Lour. with the technologies of silica gel, microporous resin, Rp-18, and Sephadex LH-20 column chromatography. It was identified as 2, 4, 6, 1′, 3′, 6′-O-hexaisovaleryl sucrose by 1D NMR, 2D NMR, high-resolution mass spectrometry, and acid hydrolysis method. Its mass spectrometry fragmentation behaviors were analyzed using high-resolution mass spectrometry and found that compound 1 was easy to break the glycosidic bond to produce the fragment at m/z 415. The ion at m/z 415 continued to eliminate the isovaleryl group as neutral or non-neutral form to generate a series of daughter ions. Compound 1 could inhibit NO production on LPS-induced neuroinflammatory responses in BV2 microglial cells at the concentrations of 5, 10, and 20 μmol·L^-1 to exhibit neuroprotective effect. Its half maximal inhibition rate of NO was measured to be 13.96 ± 0.78 μmol·L^-1.

Through literature analysis, the advantages of oral pharmaceutical vehicles in solving the temporary dispensing problems for special populations are summarized. Detailed introduction is made on the research, development, production, use, and regulatory experience of oral pharmaceutical vehicles in the United States, as well as the current research progress, achievements, and challenges faced by domestic oral pharmaceutical vehicles. The United States has formed a mature system in the field of oral pharmaceutical vehicles, and China can learn from the experience of the United States to improve relevant laws and policies, promote the establishment of technical guidance principles and technical standards for the use of oral pharmaceutical vehicles in temporary dispensing, and accelerate its clinical use.

Immune checkpoint inhibitors (ICIs) have emerged as critical agents in cancer immunotherapy; however, their resistance and limited response in most patients pose significant challenge. The gut microbiota, as a pivotal immune regulator, has been increasingly recognized for its role in enhancing the therapeutic efficacy of ICIs. Studies demonstrate that fecal microbiota transplantation or transplantation of specific bacterial strains can directly reshape the gut microbiota composition, thereby improving ICI therapeutic outcomes. Furthermore, dietary interventions, prebiotics, and postbiotics have shown potential in augmenting the anti-tumor effects of ICIs through gut microbiota modulation. Despite these promising findings, further investigations are required to optimize microbiota-based strategies and therapeutic protocols. This review highlights the critical role of gut microbiota modulation in ICI-based cancer therapy and explores its clinical applications, offering both practical insights and theoretical foundations for improving immunotherapy outcomes against various cancers.

Fourteen compounds including two new compounds were isolated from Kronopolites svenhedini (Verhoeff). These structures were identified as kronoponit A (1), kronoponit B (2), neoechinulin A (3), 2-(1, 1-dimethyl-2-propen-1-yl)-1H-indole-3-carboxaldehyde (4), uracil (5), p-hydroxy phenyl ethylamine (6), p-hydroxyphenylacetic acid (7), p-hydroxybenzoic acid (8), p-ethylbenzoic acid (9), 2-methyl-1, 4-benzenediol (10), 1, 2, 4-benzenetriol (11), gallic acid (12), gallic acid-3-methyl ether (13), and 4-methoxy-3, 5-hydroxybenzoic acid (14) by spectroscopic methods and literature. Among them, compounds 1 and 2 are new, while compounds 3-14 are reported here for the first time from K. svenhedini.

In this study, licorice-derived vesicle-like particles (LVLPs) were used as carriers, and licochalcone-A (LCA), a signature active ingredient of the same source, was used as a model drug to construct a drug-loaded LVLP@LCA nanodelivery system, and to characterize and evaluate its in vitro properties and anti-inflammatory activity. Licochalcone-A (LCA), a signature active ingredient of traditional Chinese medicine from the same source, was used as a model drug to construct a drug-loaded exocyst-like nano-delivery system, LVLP@LCA, and its in vitro properties and anti-inflammatory activities were characterized and evaluated. The LVLP@LCA nanodelivery system was prepared by extracting the exocyst-like nanoparticles by gradient centrifugation and loading the anti-inflammatory drug LCA by ultrasonication. The LVLP@LCA nanoparticles were prepared with a particle size of about 160 nm and a tea saucershaped bilayer structure, with a high encapsulation rate and drug loading capacity. The in vitro results showed that LVLP@LCA further enhanced the ability of LCA to inhibit the proliferation of inflammatory cells and reduce the levels of ROS and NO in inflammatory cells. Meanwhile, ELISA and qRT-PCR results showed that LVLP@LCA significantly reduced the secretion and mRNA expression of IL-6, IL-1β, TNF-α, CCL5, CCL17 and other related inflammatory factors and chemokines. It was demonstrated by Western blot that LVLP@LCA reduced the expression of inflammation-inducing factor interleukin 6 (IL-6) through the JAK/STAT pathway, and then inhibited the activation of inflammatory response. The present study provides a theoretical basis for the comprehensive anti-inflammatory effect of LVLP@LCA and a new way of thinking for the application of Glycyrrhiza glabra as a traditional Chinese medicine against atopic dermatitis.

Vaccines are often administered by intramuscular or subcutaneous injection. Although these methods can effectively deliver vaccine antigens to the body and trigger the immune response. However, there are also some limitations, such as injection pain, complex operation, strict transportation conditions, poor immunogenicity and stability of the vaccine. With the development of technology, skin administration has become another new way to solve the above-mentioned problems of vaccine. Among the many ways of skin administration, microneedles show unique advantages and potential. This paper briefly describes the mechanism of microneedle transdermal immunity and its advantages over traditional injection. This paper briefly describes the mechanism and advantages of transdermal immunity of microneedles, enumerates the classification of microneedles, focuses on the design concept, structural advantages and preparation technology of bionic microneedles, and analyzes its application potential in vaccines. At the same time, this paper briefly describes the application of microneedle in vaccine, including bacterial infection, viral infection, cancer treatment and current clinical application progress. The challenges and prospects of microneedle vaccine are summarized from the aspects of safety, stability and acceptability of microneedle vaccine.