As a complex autoimmune disease， rheumatoid arthritis （RA） involves immune microenvironment dysregulation resulting from excessive activation of pyroptosis， which is a crucial factor in disease progression. Based on the theory of ying-wei in traditional Chinese medicine， "ying decline and wei attack" is considered the fundamental pathogenesis of RA. Pyroptosis serves as a microscopic manifestation of this concept， suggesting a potential correlation between "ying decline and wei attack" and pyroptosis nd immune microenvironment dysregulation in RA. Accordingly， treatment principles based on this theory are proposed： in the early stage of the disease， boosting wei to consolidate the exterior， and regulating ying to dispel pathogens； in the middle and late stages， harmonizing ying to remove stagnation， and nourishing its transformational source.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis

Objective:To explore the protective effect of α-lipoic acid (LA) on radiation damage of mice cochlear ribbon synapses.Methods:Mice were divided into five groups: control group, radiation 3 d group, radiation 3 d+ LA group, radiation 14 d group and radiation 14 d+ LA group. The radiation groups were irradiated with 16 Gy, the radiation+ LA groups were given LA once a day after radiation, the control group was given the same amount of normal saline. The auditory brainstem response (ABR) of mice were measured before irradiation and sacrifice. The number of ribbon synapses were observed with immunofluorescently labeled protein ctBP2. Western blot assay was performed to obtain the semi-quantitative expression levels of otoferlin and AP-2 protein.Results:Compared with the control group, the ABR threshold of radiation groups were significantly higher ( P<0.05) with the highest value at 14 d after irradiation ( P<0.05), and the ABR threshold of the radiation+ LA groups were significantly lower ( P<0.05). The ABR threshold shifts of 12 kHz, 24 kHz at 3 d and 14 d groups had no significant difference with 8 kHz threshold shift ( P>0.05). The 32 kHz threshold shift was significantly higher than 8 kHz threshold shift ( t=-2.38, -5.48, P<0.05). The number of ribbon synapses in the radiation groups was significantly lower than that of control group ( P<0.05), with the lowest value in the radiation 14 d group. LA treatment increased the ABR value significantly ( P<0.05). AP-2 and otoferlin protein levels were significantly reduced after irradiation, especially in the radiation 14 d groups, and they were increased by the LA treatment. Conclusions:LA has protective effect on the ribbon synapses of cochlear hair cells.

Objective To investigate the reasons for leaving of contract nurses in a tertiary oncology hospital in Beijing , propose related countermeasures and improve the ways of human resource management to stabilize the nursing team .Methods Retrospective analysis combined with deep interview was used to study the reasons of nurses'leaving by reviewing their basic information .Results Leaving nurses were mostly not the household register of Beijing, younger than 26 years old, college degree, with low title and short working years. The reasons were mainly family related , such as marriage , taking care of parents or kids , high work pressure and low treatment , etc.Conclusions Hospital managers should improve human-based management and nurse's payment, as well as relieve their work pressure in order to stabilize the nursing team .