Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis.

Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

Small tissue chips with big opportunities for space medicine.

The spaceflight environment, including microgravity and radiation, may have considerable effects on the health and performance of astronauts, especially for long-duration and Martian missions. Conventional on-ground and in-space experimental approaches have been employed to investigate the comprehensive biological effects of the spaceflight environment. As a class of recently emerging bioengineered in vitro models, tissue chips are characterized by a small footprint, potential automation, and the recapitulation of tissue-level physiology, thus promising to help provide molecular and cellular insights into space medicine. Here, we briefly review the technical advantages of tissue chips and discuss specific on-chip physiological recapitulations. Several tissue chips have been launched into space, and more are poised to come through multi-agency collaborations, implying an increasingly important role of tissue chips in space medicine.

Recent advances in chemical synthesis, biocatalysis, and biological evaluation of diosgenin derivatives - A review.

Extracting organic compounds from plants and developing derivatives are essential methods for drug discovery. Diosgenin, extracted from Dioscoreaceae plants, is a type of spirostan steroid with various biological effects, including anti-inflammation, neuro-protection, and apoptosis-induction. Many researchers committed their work to the chemical semi-synthesis of diosgenin derivatives to improve diosgenin's therapeutic bioavailability and expand its range of applications in disease treatment and prevention. Biotransformation, a mild whole-cell biocatalysis method, also made crucial contributions to the structural diversity of diosgenin analogs in recent years. Although the structural modification of diosgenin has made significant progress, it lacks a comprehensive review. Here, we review the chemical modification and biotransformation of diosgenin along with the biological evaluation of diosgenin derivatives to provide a reference for the structural modification strategy and pharmaceutical application of diosgenin derivatives.

Synthesis and biological evaluation of celastrol derivatives as potent antitumor agents with STAT3 inhibition.

Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines. The western blotting analysis showed that compound 4 m, the most active derivative, could suppress the STAT3's phosphorylation as well as its downstream genes. SPR analysis, molecular docking and dynamics simulations' results indicated that the 4m could bind with STAT3 protein more tightly than celastrol. Then we found that the 4m could block cell-cycle and induce apoptosis on HCT-116 cells. Furthermore, the anti-tumour effect of 4m was verified on colorectal cancer organoid. This is the first research that discovered effective STAT3 inhibitors as potent anti-tumour agents from celastrol derivatives.

Aspirin inhibits prostaglandins to prevents colon tumor formation via down-regulating Wnt production.

According to numerous epidemiological studies, aspirin is a non-steroidal anti-inflammatory drug (NSAID) that reduces the occurrence and mortality of colorectal cancer (CRC). However, the underlying mechanisms are not well identified. In an effort to fill these gaps, we administered aspirin on mice one day before induction in an azoxymethane (AOM)/dextran sulfate sodium (DSS) induced CRC model. In this study, we assessed the effects of aspirin on tumorigenesis and tumor cell proliferation. Multi-layer analyses were carried out to identify changes in cytokines, metabolites, level of gene expressions, and proteins associated with tumorigenesis and aspirin treatment. The results showed that aspirin-treated mice developed fewer colon tumors in response to AOM/DSS, and aspirin can actively block cyclooxygenase (COX) metabolism and reduce levels of pro-inflammatory cytokines. In addition, the transcriptomic and proteomic analyses both indicated that aspirin has an inhibitory effect on the Wnt pathway. The in vitro results further indicated that aspirin inhibits WNT6 production, possibly by suppressing its transcription factor NR4A2, which in turn is regulated by prostaglandin E2, thereby ultimately inhibiting the Wnt pathway. These findings improve our understanding of the mechanisms behind aspirin's chemoprevention effect on CRC.

Celastrol in metabolic diseases: Progress and application prospects.

Metabolic diseases are becoming increasingly common in modern society. Therefore, it is essential to develop effective drugs or new treatments for metabolic diseases. As an active ingredient derived from plants, celastrol has shown great potential in the treatment of a wide variety of metabolic diseases and received considerable attention in recent years. In reported studies, the anti-obesity effect of celastrol resulted from regulating leptin sensitivity, energy metabolism, inflammation, lipid metabolism and even gut microbiota. Celastrol reversed insulin resistance via multiple routes to protect against type 2 diabetes. Celastrol also showed effects on atherosclerosis, cholestasis and osteoporosis. Celastrol in treating metabolic diseases seem to be versatile and the targets or pathways were diverse. Here, we systematically review the mechanism of action, and the therapeutic properties of celastrol in various metabolic diseases and complications. Based on this review, potential research strategies might contribute to the celastrol's clinical application in the future.