Latest ArticlesRhei Radix et Rhizoma is one of the genuine medicinal materials in Sichuan. Its original species are Rheum palmatum, Rh. tanguticum, and Rh. officinale, recorded by Chinese Pharmacopoeia (2025 Edition). However, there are many cases of multi-origin mixing and adulterant incorporation in the current commercially available Rhei Radix et Rhizoma, and the variety origin needs to be clarified urgently. In this study, the ndhF-rpl32 region of chloroplast genomes, as specific DNA barcode reported previously, was selected and confirmed. The VPCR method was established to identify the authenticity and origin of rhubarb medicinal materials, decoction pieces and Chinese patent medicines, in the process of optimizing DNA extraction procedure, amplification system and amplification procedure. Compared with the traditional PCR method, the amplification procedure has been refined through a VPCR heating model, curtailing the detection from 1.5 h to 30 min. The 85 batches of samples collected from the circulation area were tested by VPCR method, including 30 batches of medicinal materials, 40 batches of decoction pieces and 15 batches of Chinese patent medicines which contain Rhei Radix et Rhizoma. The experimental results showed that 31 batches are Rh. tanguticum (including 18 batches of medicinal materials, 10 batches of decoction pieces and 3 batches of Chinese patent medicines), 36 batches are Rh. officinale (including 1 batches of medicinal materials, 25 batches of decoction pieces and 10 batches of Chinese patent medicines) and 13 batches are Rh. palmatum (including 8 batches of medicinal materials and 5 batches of decoction pieces). The pass rate is 94.1%. Three batches of rhubarb medicinal materials (No. CD1, CD2, CD3) and two batches of Chinese patent medicines (No.Z4 tablet, No.Z12 granule) were determined to be Rh. franzenbachii Munt, as one of counterfeit Rhei Radix et Rhizoma varieties. The VPCR method established in this study can be used as supplement to rhapontin TLC inspection test of Rhei Radix et Rhizoma in Chinese Pharmacopoeia (2025 Edition) and standardize the market for this clinical medication as well as improve the safety of Rhei Radix et Rhizoma.
Helicobacter pylori (H. pylori) infects 48.5% of the global population, with approximately 42.8% in China and is linked to chronic gastritis and gastric cancer. Current mainstream antibiotic therapies against H. pylori are limited in clinical application due to antibiotic resistance and high recurrence rates. Consequently, there is an urgent need to develop novel therapeutic strategies. Research indicates that persistent H. pylori infection relies on its immune evasion mechanisms. Outer membrane vesicles (OMVs) serve as critical mediators in pathogen-host interactions, facilitating multiple immune escape strategies by delivering virulence factors, nucleic acids, and other substances. Deciphering the mechanisms of OMVs-mediated immune evasion in H. pylori is pivotal for overcoming the bottlenecks in OMVs-based H. pylori vaccine development and devising novel targeted therapeutic strategies. This review synthesizes recent research advances in OMVs-driven immune evasion, analyzes challenges in translational applications, and proposes future directions to inform innovative anti-H. pylori strategies.
Pruritus is an important physiological sensation mediated by the somatosensory system, and its clinical significance is increasingly recognized. Based on the underlying mechanisms, pruritus can be classified into histaminergic and non-histaminergic types. Non-histaminergic pruritus constitutes the major form of most chronic pruritus conditions and often shows poor response to conventional antihistamines. The gastrin-releasing peptide receptor (GRPR) in the spinal cord, serving as a pruritus-specific receptor, plays a critical role in the transmission of non-histaminergic pruritic signals. The κ-opioid receptor (KOR) and the μ-opioid receptor (MOR) exert opposite effects in pruritus regulation: MOR activation promotes pruritus, whereas KOR activation produces inhibitory effects. This review systematically elaborates on the multiple molecular mechanisms through which KOR inhibits pruritus, with a focus on the direct inhibition of GRPR function via protein kinase Cδ (PKCδ)-mediated phosphorylation, interference with intracellular calcium signaling, potential modulation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and comprehensive regulation of pruritic pathways through signaling molecules such as Gβγ and β-arrestin 2. Together, these mechanisms constitute the basis for KOR-mediated regulation of pruritic signals at the spinal level. Although KOR agonists (e.g., TRK-820, CR845) have shown therapeutic potential for chronic pruritus in clinical studies, translational challenges such as species differences and cross-talk among signaling pathways warrant further attention. In-depth elucidation of the KOR regulatory network not only provides novel insights into the physiological and pathological mechanisms of pruritus but also establishes a solid theoretical foundation for the development of novel, highly-targeted anti-pruritus drugs with fewer side effects.
Recent advances in understanding the modulatory functions of gut microbiota on human diseases facilitated our focused attention on the contribution of the gut to the pathophysiological alterations of many extraintestinal organs. Tryptophan-derived indole metabolites have become crucial signaling molecules in the gut-organ axis, playing a core role in anti-inflammation, immune homeostasis, and maintaining mitochondrial function by activating the aryl hydrocarbon receptor and pregnane X receptor. This review systematically explores the regulatory mechanisms of indole metabolites on host diseases through the gut-liver axis, gut-brain axis, gut-heart axis, and gut-lung axis, providing a new theoretical perspective for understanding the interaction between the gut microbiota and the host and developing new strategies for the prevention and treatment of related diseases.
Antibody-drug conjugates (ADC) are a type of innovative and highly effective anti-cancer drugs. They connect the high specificity of monoclonal antibody drugs with the efficient killing ability of small molecule toxins through a linker, effectively enhancing tumor targeting and reducing toxic side effects. As a highly promising innovative therapy in the field of cancer treatment, ADC have brought new hope to cancer patients. However, the issue of tumor permeability has become a key factor restricting the full exertion of their efficacy. This review introduces the mechanism of action and structural optimization strategies of ADC, analyzes the complex factors that hinder the permeation of ADC in the tumor microenvironment, and discusses the drug administration strategies to improve ADC permeability. Through the systematic review of relevant research progress, it provides theoretical basis and practical guidance for promoting the further development of ADC in tumor treatment.
Bacterial and parasitic infections rank as the second leading cause of death globally. The persistent rise in antibiotic resistance, particularly against β-lactams, vancomycinand methicillin, poses a significant challenge to public health. The World Health Organization (WHO) has prioritized the fight against antibiotic resistance, recognizing the urgent need for new targets and the development of novel antibiotics. Given that many potential drugs focus on pathogens prioritized by the WHO, which often share characteristics with existing antibiotic classes, fostering resistance, there is an imperative requirement to identify new targets and develop agents that specifically address these challenges. Bacterial peptidoglycan, with its specificity for bacteria and essential role in their survival, has become a focal point of research. Due to the enzymes involved in peptidoglycan biosynthesis being exclusive to bacteria, they represent ideal targets for the discovery of new antimicrobials. Inhibiting these enzymes offers an optimal inhibition profile, where the inhibitors are inactive towards eukaryotic cells but effectively combat bacterial infections. The aim of this review is to introduce the advancements in the synthesis of a series of inhibitors targeting the bacterial transferase MraY, which catalyzes the first membrane-bound step in peptidoglycan biosynthesis. Currently, there are no antibiotics in clinical use that target MraY. By inhibiting MraY, the hope is to mitigate the development of resistance. Natural inhibitors of MraY, based on the aminoarabinosyluridine scaffold, have been known for their biological activity. However, due to their limited antibacterial efficacy, several research groups have embarked on the development of simplified analogues to enhance their therapeutic potential.
QS-21 is an immunologically active saponin-based immunostimulant extracted from the bark of the South American soapbark tree (Quillaja saponaria, QS). It consists of four structural domains: Quillaic acid, a trisaccharide side chain, a tetrasaccharide chain, and a pseudodimeric acyl chain. It exists in two isomeric forms, QS-21-Api and QS-21-Xyl, among which the C-4 aldehyde group and the acyl side chain are the key moieties for adjuvant activity. In terms of its immunological mechanism, QS-21 can simultaneously activate Th1/Th2-type immune responses, enhance the cross-presentation of antigens by dendritic cells, and activate the MAPK (mitogen-activated protein kinase) pathway in T cells as well as the NLRP3 (NOD-like receptor protein 3) inflammasome. It exhibits particularly prominent performance in inducing cellular immunity. This article summarizes the currently developed composite adjuvant systems such as AS01, AS02, Matrix-M, AS15, and GLA-LSQ, along with their applications in vaccines including the malaria vaccine Mosquirix and the shingles vaccine Shingrix. Regarding issues such as supply shortages associated with natural extraction, technologies for chemical total synthesis, semi-synthesis, and yeast-based biosynthesis are making gradual breakthroughs, Strategies including some derivatives (such as VSA-1 and TQL1055) also provide references for the development of new vaccines and the prevention and control of infectious diseases as well as immunotherapy.
As indispensable medications in the medical field, antibiotics face severe challenges such as high pollution and high energy consumption in their traditional chemical synthesis processes. The novel enzymatic catalytic process, leveraging the catalytic properties of enzymes and the advantages of environmental friendliness, has emerged as a new direction for the green development of the antibiotic industry. This paper focuses on the application progress of the novel enzymatic catalytic process in the green synthesis of antibiotics, systematically elaborates on its catalytic mechanism, and analyzes the specific applications and advantages of this process in the production of antibiotics such as β-lactams, aminoglycosides, and macrolides. Meanwhile, it points out the issue that catalyst residues during the production process affect the quality and safety of pharmaceutical products, and discusses the current challenges confronted by the novel enzymatic catalytic process for antibiotics. Finally, by applying cutting-edge technologies including synthetic biology and artificial intelligence, this paper provides a theoretical basis and solutions for breaking through existing technical limitations and promoting the green upgrading of the antibiotic industry.
The current quality control standards for traditional Chinese medicine (TCM) are relatively simplistic, as relying solely on the quantification of chemical components fails to fully interpret the quality connotation of multi-effect medicinal substances. In contrast, phase-state analysis, which focuses on the physical forms of multiple components, is considered to provide a new perspective for researching the material basis of the efficacy of TCM. This article focuses on the challenges in quality control of multi-efficacy TCM, systematically analyzes the limitations of current standards in reflecting its multi-functional nature, and reviews research approaches and current progress on the role of physicochemical state in the material basis of TCM efficacy. It elaborates on the mechanism of self-assembly via non-covalent bonds and the structure-function synergy. Building on this, a new "top-down and bottom-up" integrated strategy for quality control research of multi-efficacy TCM is proposed. This aims to promote innovation in TCM quality control models, guide rational drug selection, and provide a scientific basis for constructing a quality evaluation system that aligns with the characteristics of TCM.
With the increasing severity of bacterial resistance issues, β-lactamase, as the key enzyme mediating resistance to β-lactam antibiotics, requires rapid and accurate detection that plays significant importance for clinical treatment and antimicrobial resistance surveillance. In recent years, the rapid development of proteomic technologies has provided novel strategies for high-throughput identification of β-lactamases. This article reviews the application progress of mass spectrometry-based proteomic technologies in β-lactamase detection, compared with traditional phenotypic detection and genetic sequencing methods, proteomic technologies enable direct capture of enzyme expression-level information, offering multidimensional data support for elucidating the association between resistant phenotypes and protein functions. Furthermore, advancements in targeted proteomics have enhanced detection sensitivity and specificity, facilitating the exploration of personalized anti-infective therapies. Looking forward, through the integration of artificial intelligence-assisted analysis and the development of miniaturized high-throughput detection devices, proteomic technologies are expected to play a more prominent role in real-time antimicrobial resistance monitoring and precision medicine.
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