This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

This paper aimed to explore the intestinal toxicity of Euphoriae Ebracteolata Radix(EER) before and after being processed with Mongolian medicine Hezi Decoction(HZD) and the toxicity-reducing mechanism of this processing method. The intestinal toxicity in rats treated with unprocessed EER and HZD-processed EER extracts via 95% ethanol was compared. The comparison was based on several indicators, including fecal volume, serum diamine oxidase(DAO) and D-lactate(D-LA) levels, the water content of various intestinal segments and their contents, and inflammatory factor levels in intestinal segments. Tandem mass tag(TMT) quantitative proteomics technology was employed to analyze the key proteins associated with changes in intestinal toxicity between unprocessed EER and HZD-processed EER. The results indicated that compared with the blank group, unprocessed EER significantly increased the fecal volume, serum DAO and D-LA levels, water content of the ileal segment and its contents, as well as the release levels of inflammatory factors, including tumor necrosis factor(TNF-α) and interleukin-1 beta(IL-1β) in the ileal segment of rats(P<0.05), indicating that EER can cause diarrhea, increase intestinal permeability, and induce intestinal inflammation. Compared with those in the unprocessed EER group, all indicators in the HZD-processed EER group were significantly reduced(P<0.05). The TMT quantitative proteomics analysis revealed that a total of 6 487 proteins were identified in the rat ileum tissue. Compared to the blank group, 182 proteins exhibited significant changes in the unprocessed EER group, while 907 proteins in the HZD-processed EER group showed significant changes. The intersection of the differential proteins between the two groups identified 38 common proteins. Among them, the protein levels of intestinal barrier tight junction protein claudin3, squalene monooxidase(Sqle), clusterin, Na~+/H~+ exchange regulatory cofactor NHE-RF3(Pdzk1), and Y+L amino acid transporter 1(Slc7a7) exhibited significant changes before and after processing, and these changes were closely related to intestinal barrier function. Compared with the blank group, the expression of claudin3, Pdzk1, and Slc7a7 in the raw product group was significantly down-regulated(P<0.05),while the expression of Sqle and clusterin was significantly up-regulated(P<0.05).Compared with the raw product group, the expression of claudin3, Pdzk1, and Slc7a7 in the processed product group of HZD was significantly up-regulated(P<0.05), while the expression of Sqle and clusterin was significantly down-regulated(P<0.05). Western blot was used to detect the expression level of claudin 3 in the ileum of rats in each group. The results show that compared to that in the blank group, the expression level of claudin 3 in the unprocessed EER group was significantly reduced(P<0.01); compared to that in the unprocessed EER group, the expression level of claudin 3 in the HZD-processed EER group was significantly increased(P<0.01). This finding aligned with the proteomic outcomes, indicating that claudin 3 protein levels could serve as a crucial indicator for intestinal damage caused by EER. In summary, HZD-processed EER can reduce EER's intestinal toxicity, and the primary mechanism for its alleviation of intestinal barrier damage is the regulation of the intestinal barrier tight junction protein claudin 3 and other intestinal-related proteins.
Animals ; Drugs, Chinese Herbal/adverse effects* ; Proteomics ; Rats ; Male ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Intestinal Mucosa/drug effects* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index