The human blood-brain barrier (BBB) is a complex multi-dimensional reticular barrier system composed of cerebral microvascular endothelial cells, pericytes, astrocytes and a variety of neurons. The conventional in vitro cell culture model fails to truly present the dynamic hemodynamics of BBB and the interaction between neurons. And it is even more impossible to explore brain-related multi-organ diseases, which brings huge obstacles to explore diseases of the central nervous system and the interaction between brain-related multi-organs, and evaluate drug efficacy. Miniaturized microfluidics based BBB chips are being commonly used to co-culture a variety of cells on a small-sized chip to construct a three-dimensional (3D) BBB or BBB-related organ disease models. By combining with other electrophysiological, biochemical sensors or equipment and imaging systems, it can in real time and quickly screen disease-related markers and evaluate drug efficacy. This review systematically summarized the research progress of in vitro BBB and BBB-related organ chips, and analyzed the obstacles of BBB models in depth. Parallelly combined with the current research trends and hot spots, we give the further improvement measures of microfluidic BBB chips.
Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens ‘Variegata’. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.
G protein-coupled receptors (GPCRs) widely exist in vivo and participate in many physiological processes, thus emerging as important targets for drug development. Approximately 30% of the Food and Drug Administration (FDA)-approved drugs target GPCRs. To date, the ‘one disease, one target, one molecule’ strategy no longer meets the demands of drug development. Meanwhile, small-molecule drugs account for 60% of FDA-approved drugs. Traditional Chinese medicine (TCM) has garnered widespread attention for its unique theoretical system and treatment methods. TCM involves multiple components, targets and pathways. Centered on GPCRs and TCM, this paper discusses the similarities and differences between TCM and GPCRs from the perspectives of syndrome of TCM, the consistency of TCM’s multi-component and multi-target approaches and the potential of GPCRs and TCM in the development of novel drugs. A novel strategy, ‘simultaneous screening of drugs and targets’, was proposed and applied to the study of GPCRs. We combine GPCRs with TCM to facilitate the modernisation of TCM, provide valuable insights into the rational application of TCM and facilitate the research and development of novel drugs. This study offers theoretical support for the modernisation of TCM and introduces novel ideas for development of safe and effective drugs.
Screening for pulmonary nodules (PN) using low-dose CT has proven effective in reducing lung cancer (LC) mortality. However, current treatments relying on follow-up and surgical excision fail to fully address clinical needs. Pathological angiogenesis plays a pivotal role in supplying oxygen necessary for the progression of PN to LC. The interplay between hypoxia and angiogenesis establishes a vicious cycle, rendering anti-angiogenesis therapy alone insufficient to prevent PN to LC transformation. In traditional Chinese medicine (TCM), PN is referred to as “Feiji,” which is mainly attributed to Qi and blood deficiency, correspondingly, the most commonly prescribed medicines are Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (huang qi) (AR) and Angelica sinensis (Oliv.) Diels (dang gui) (ARS). Modern pharmacological studies have demonstrated that AR and ARS possess immune-enhancing, anti-tumor, anti-inflammatory, and anti-angiogenic properties. However, the precise mechanisms through which AR and ARS exert anti-angiogenic effects to delay PN progression to LC remain inadequately understood. This review explores the critical roles of hypoxia and angiogenesis in the transition from PN to LC. It emphasizes that, compared to therapies targeting angiogenic growth factors alone, AR, ARS, and their compound-based prescriptions offer additional benefits. These include ameliorating hypoxia by restoring blood composition, enhancing vascular structure, accelerating circulation, promoting vascular normalization, and blocking or inhibiting various pro-angiogenic expressions and receptor interactions. Collectively, these actions inhibit angiogenesis and delay the PN-to-LC transformation. Finally, this review summarizes recent advancements in related research, identifies existing limitations and gaps in knowledge, and proposes potential strategies and recommendations to address these challenges.