Endogenous gases have attracted much attention due to their potent applications in disease therapies. The combined therapy, including gaseous molecules and other medicines that can create synergistic effects, is a new way for future treatment. However, due to the gaseous state, gas utilization in medical service is still limited. To pave the way for future usage, in this work, an amphiphilic block copolymer containing nitrobenzyl ether, 3-hydroxyflavone (3-HF) derivatives and ether linker was constructed. The nitrobenzyl ether group endows the polymer with a photo-responsive character. Upon light illumination, 3-HF derivatives can be triggered for carbon monoxide (CO) release. The ether linker can also be released emitting formaldehyde (FA). The self-assembly induced micelle can encompass medicine, e.g., doxorubicin (DOX), into it and a controlled release of DOX can be realized upon light illumination. As far as we know, there is no report on the combination donor of CO and DOX and this is the first attempt on the co-release of CO, FA and DOX.

Aconiti Lateralis Radix Praeparata (Fu Zi) is the processed lateral root of Aconitum carmichaelii Debx, which is widely used in emergency clinics. Poisoning incidents and adverse reactions occur with the improper intake of Fu Zi. Metabolic characteristics of aconitum alkaloids of Fu Zi may vary, and the effects of Fu Zi in healthy and Long QT syndrome (LQTS) patients is unknown. In this experiment, 24 Sprague Dawley rats were randomly divided into three groups: 2.0, 1.0, and 0.5 g/kg dose groups, and blood samples were collected after the oral administration of Fu Zi extract. We used an ultra-high performance liquid chromatography-tandem mass spectrometry system to detect the concentrations of six aconitum alkaloids. Cell toxicity, calcium imaging, and patch-clamp recordings of human induced pluripotent stem cells-cardiomyocytes (hiPSC-CMs) of aconitine in healthy and LQTS were observed. We found that the AUC_(0–48h), C_max, and t_1/2 of the six compounds increased with the multiplicative dosages; those in the high group were significantly higher than those in the low group. Aconitine concentration-dependently decreased the amplitude, which has no significant effect on the cell index of normal hiPSC-CMs. Aconitine at 5.0 μM decreased the cell index between 5–30 min for LQTS hiPSC-CMs. Meanwhile, aconitine significantly increased the frequency of calcium transients in LQTS at 5 μM. Aconitine significantly shortened the action potential duration of human cardiomyocytes in both normal and LQTS groups. These results show metabolic behaviors of aconitum alkaloids in different concentrations of Fu Zi and effects of aconitine in healthy and LQTS patients.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

Selenium, an essential trace element in the human body, is present in the form of selenocysteine (Sec) within 25 selenoproteins, including selenoprotein N, selenoprotein P, and glutathione peroxidases (GPXs). An increasing number of studies have shown that selenoproteins resulting from selenium metabolism exert a significant effect on diverse immune cells. For instance, both selenoprotein K and GPX4 are intricately involved in the initiation and resolution of pro‐inflammatory responses in granulocytes (PMN). The function of dendritic cells (DCs) exhibits a specific association with the expression of selenoproteins. Methionine sulfoxide reductase B1 (MSRB1) can facilitate lipopolysaccharide (LPS) in stimulating bone marrow‐derived macrophages (BMDM), induce the production of anti‐inflammatory cytokines interleukin‐10 (IL‐10) and interleukin‐1 receptor antagonist (IL‐1RA), and thereby partake in immune activities. The roles of selenoproteins in immune cells underscore their significance and complexity in the overall physiological process. In particular, their involvement in tumor immunity warrants in‐depth exploration. In solid tumors, the process by which cancer cells generate selenoproteins, especially GPX4, through selenium metabolism constructs a defense mechanism against ferroptosis. This process is highly reliant on the capacity of cancer cells to take up selenium independently, as well as the activation of selenium metabolic pathways such as the trans‐selenation pathway and the breakdown of inorganic selenium compounds. In the autophagy mediated by copper and erastin (a ferroptosis inducer), the autophagy receptors TAX1BP1 and SQSTM1 can promote the degradation of GPX4, effectively reducing the resistance of cancer cells to ferroptosis. This distinctive mechanism has opened up a novel perspective for research and offered potential therapeutic targets in the field of cancer treatment. In this review, we conduct a comprehensive and in‐depth analysis of the roles played by selenoproteins derived from selenium metabolism in the regulation of immune cells associated with immune diseases. Moreover, we elaborate in detail on the effects of GPX4 in relation to ferroptosis in solid tumors under the influence of autophagy‐mediated immunomodulation.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

Proanthocyanidin A₂ (PA₂) is a class of bioactive small-molecule natural polyphenols, while selenocysteine (Sec) represents an essential functional selenium-containing amino acid in humans and has emerged as a cutting-edge research hotspot in the field of natural bioactive factors. This review systematically summarizes the natural resource distribution and biological signaling pathways of PA₂, as well as the in vivo metabolic profiles of Sec. It further elaborates on the core physiological and pathological processes co-regulated by PA₂ and Sec, including oxidative stress homeostasis, inflammatory immune responses, and metabolic reprogramming. Malignant tumors, severe diseases triggered by disrupted organismal homeostasis, serve as the primary research model for exploring the synergistic regulatory effects of PA₂ combined with Sec. Accumulating evidence has validated the independent anti-tumor efficacy of PA₂ and Sec in respective research domains; nevertheless, studies investigating their synergistic bioactivities remain scarce. Starting from the natural resource distribution of PA₂ and the respective core biological functions of the two agents, this work systematically dissects their individual roles in modulating oxidative stress, inflammatory responses, tumor malignant proliferation and apoptosis, and proposes putative synergistic regulatory mechanisms with hypothetical mechanistic validation. The findings are expected to provide theoretical references and innovative research strategies for developing combinatorial interventions of natural polyphenols and selenocysteine against tumors and related disorders, as well as for constructing antioxidant damage defense systems.