1.Herbal Textual Research and Modern Research Progress of Ostreae Concha
Hongyi ZHANG ; Bin WANG ; Jiawen LIU ; Yuan HU ; Lin CHEN ; Youping LIU ; Hongping CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):223-234
By consulting relevant literature of ancient herbal books and processing specifications, this paper made a systematic research and analysis of Ostreae Concha, including the name, producing area, harvesting, quality, historical evolution of processing, relevant processing specifications, modern processing technology, and changes in chemical composition and pharmacological effects before and after processing, in order to provide documentary evidence for the research on processing technology and the establishment of quality standards. According to the textual research, it is known that Ostreae Concha has a long history of being used in medicine, and there have been many aliases and local names in each historical period. Shennong's Classic of the Materia Medica(Shennong Bencaojing) began to use Muli as the correct name, which has continued to use to today, and there were also aliases such as Muge, Zuogu Muli and Haoke. Ostreae Concha has a wide range of localities and irregular harvesting periods. The ancients believed that its left shell was of superior quality, but this has not been seen in modern. And there were many kinds of processing methods of Ostreae Concha, such as grinding, roasting, calcining, frying, simmering, quenching and so on, and the calcining was still in use. The different editions of Chinese Pharmacopoeia from 1963 to 2020 contain only calcined Ostreae Concha, and the local processing specifications mainly include three kinds of processed products(calcined products, salt-soaked products and vinegar-soaked products). Modern processing research mainly focuses on process optimization, changes in chemical composition and pharmacological effects, and the research methods are relatively single. Overall, there are currently issues such as inconsistent processing standards, unclear process parameters and imperfect quality standards, which are not conducive to the quality control and standardized clinical use of Ostreae Concha. Therefore, it is necessary to further investigate the pharmacological substance basis of Ostreae Concha and its processed products in order to elucidate the processing mechanism, standardize the processing technology and improve the quality standard.
2.Fitting Degrees of Animal Models of Chronic Glomerulonephritis with Clinical Characteristics in Western Medicine and Traditional Chinese Medicine
Siqing WU ; Lin GUO ; Beibei ZHANG ; Mingsan MIAO ; Jinxin MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):259-264
Chronic glomerulonephritis (CGN) is a common clinical chronic glomerular disease caused by autoimmune reaction, the pathogenesis of which is complex and has not been fully elucidated. There is no specific treatment method in modern medicine. The establishment of an animal model of CGN in accordance with its characteristics in western medicine and traditional Chinese medicine will help to reveal the pathogenesis of CGN, rate drugs, and improve the treatment plan. Based on the clinical diagnostic criteria of CGN, the paper establishes the syndrome differentiation criteria of CGN for Chinese and western medicine. Through summarizing the literature on animal models of CGN and making a further analysis, it is found that the CGN models are mainly modeled using rats with the methods of single-factor induction or two-factor induction, and the main manifestation of the disease characteristics is nephritis-related symptoms. The single-factor-induced or two-factor-induced CGN rat models have a high fitting degree with the clinical characteristics in western medicine, but the fitting degree is insufficient with the clinical characteristics in traditional Chinese medicine. In addition, the CGN models with syndromes of traditional Chinese medicine are dominated by Qi deficiency in the spleen and kidney and Qi deficiency in the lung and kidney, while models for Yang deficiency in the spleen and kidney, Yin deficiency in the liver and kidney, and deficiency of both Qi and Yin are slightly insufficient. Therefore, it is important to prepare a new and improved animal model of CGN, so that a preclinical model can be provided for the exploration of the pathogenesis of CGN in western medicine and traditional Chinese medicine and its therapeutic research.
3.Effect and mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance in rats with type 2 diabetes mellitus
Yuxin HONG ; Lei ZHANG ; Mingxue ZHOU ; Sinai LI ; Li LIN ; Meng ZHANG ; Zixuan GUO ; Weihong LIU
China Pharmacy 2025;36(1):24-29
OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group, model group, Qingxue xiaozhi jiangtang formula low-dose and high-dose groups (6.525, 13.05 g/kg, calculated by raw material) and metformin group (positive control, 0.18 g/kg), with 8 rats in each group. Administration groups were given relevant medicine intragastrically; normal control group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 6 weeks. Body mass and fasting blood glucose (FBG) were determined, and oral glucose tolerance test was conducted. Serum fasting insulin (FINS) level was measured to calculate the insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI). Additionally, the level of serum lipids, liver function, oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase (PERK) and forkhead box O1 (FOXO1) protein in liver tissue of rats were determined. RESULTS Compared with model group, the body weight, ISI, the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group (P<0.05); FBG, blood glucose level at 120 minutes of glucose loading, area under the curve of glucose, FINS, HOMA-IR, low-density lipoprotein cholesterol, total cholesterol, triglyceride, alanine transaminase, aspartate transaminase, alkaline phosphatase, malondialdehyde, interleukin-6, tumor necrosis factor-α, and C-reactive protein levels were significantly reduced (P< Δ0.05); the pathological damage of liver tissue had significantlyimproved, and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased (P<0.05). CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism, inflammation factor and oxidative stress levels, and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.
4.Mechanism of Modified Shaofu Zhuyutang in Antagonising Ectopic Endometrial Tissue Fibrosis Based on Cellular Pyroptosis Mediated by TRL4/NF-κB/NLPR3 Signaling Pathway
Zuoliang ZHANG ; Jiaxing WANG ; Wanrun WANG ; Xiangyu LIN ; Bin YUE ; Zhirui ZHANG ; Yinan WANG ; Yaling YANG ; Dongqing WEI ; Cancan HUANG ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):19-28
ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 (TRL4/NF-κB/NLPR3) signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group (n = 12) and a modeling group (n = 60). The rats in the sham-operated group underwent a caesarean section, while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling, the animals were randomly divided into the model group, progesterone group (0.25 mg·kg-1), and modified Shaofu Zhuyutang low-, medium-, and high-dose groups (7.5, 15, 30 g·kg-1), with 12 animals in each group. After 4 weeks of drug administration, voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection, and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). Immunohistochemistry (IHC) was used to detect the protein expression area of tumor necrosis factor-related factor 6 (TRAF6) and NLPR3 in the endometrial tissues. Immunofluorescence (IF) was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D (GSDMD) in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4, myeloid differentiation factor 88 (MyD88), TRAF6, NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of TRL4, MyD88, TRAF6, NF-κB, and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group, rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18, IL-1β, TNF-α, and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased, and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4, MyD88, TRAF6, NF-κB p65, p-NF-κB p65, and NLPR3 proteins, along with the expression of TRL4, MyD88, TRAF6, NF-κB, and NLPR3 mRNA, were significantly increased (P<0.01). Compared with the model group, rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity, longer heat pain latency, the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18, IL-1β, TNF-α, and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased, and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4, MyD88, TRAF6, p-NF-κB p65, NLPR3 proteins, and TRL4, MyD88, TRAF6, NF-κB, and NLPR3 mRNA expression were reduced (P<0.05, P<0.01). ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway, reducing NLRP3 inflammasome-induced cellular pyroptosis, antagonizing the fibrosis process in ectopic endometrial tissues, improving the inflammatory microenvironment in the pelvic cavity, and alleviating pain.
5.Mechanism of Modified Shaofu Zhuyutang in Treatment of Endometriosis Based on EGFR/PI3K/Akt Signaling Pathway
Yaling YANG ; Wanrun WANG ; Zuoliang ZHANG ; Xiangyu LIN ; Jiaxing WANG ; Cancan HUANG ; Xiujia JI ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):29-38
ObjectiveTo observe the effects of modified Shaofu Zhuyutang on key proteins of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in SD rats with endometriosis. MethodsAfter successful establishment of an endometriosis model in 60 female SD rats of SPF grade via the auto-transplantation method, the rats were randomly divided into a model group, modified Shaofu Zhuyutang high-, medium-, and low-dose groups, and a gestrinone group, with another 12 rats serving as a blank group. The blank and model groups were administered 10 mL·kg-1 normal saline, while the high-, medium-, and low-dose groups received 30, 15, and 7.5 g·kg-1 modified Shaofu Zhuyutang, respectively. The gestrinone group was administered 0.25 mg·kg-1 gestrinone suspension. After four weeks of treatment, uterine contractions were induced with 2 U of oxytocin, and the writhing response of rats was observed. After 24 h, the rats were euthanized, and the weight and volume of ectopic endometrial tissue were recorded. Hematoxylin-eosin (HE) staining was used to observe pathological changes in endometrial tissues, while the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was used to evaluate the apoptosis rate of endometrial tissues. Immunofluorescence was used to detect the relative expression areas of the B-cell lymphoma-2 gene-associated promoter (Bad) and B-cell lymphoma-2 (Bcl-2) proteins in endometrial tissues. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), and EGFR were measured by enzyme-linked immunosorbent assay (ELISA). The relative protein expression levels of EGFR, PI3K, phosphorylated PI3K (p-PI3K), Akt, and phosphorylated Akt (p-Akt) in endometrial tissues were analyzed by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of EGFR, PI3K, and Akt. ResultsCompared with the blank group, the model group showed endometrial thickening, glandular and mesenchymal hyperplasia, a significant decrease in the relative expression area of Bad in ectopic endometrial tissues, a significant increase in the relative expression area of Bcl-2, and a significant reduction in the apoptosis rate as indicated by TUNEL staining. Serum levels of IL-1β, IL-6, TNF-α, EGF, and EGFR were significantly elevated (P<0.01). The relative protein expression levels of EGFR, PI3K, p-PI3K, Akt, and p-Akt, as well as the mRNA expression levels of EGFR, PI3K, and Akt, were also significantly increased (P<0.01). Compared with the model group, the high- and medium-dose groups of modified Shaofu Zhuyutang and the gestrinone group exhibited reduced glandular and mesenchymal hyperplasia to varying degrees, with dilated glandular lumens. The number of writhing responses was significantly reduced, the latency to writhing response was significantly prolonged, and the weight and volume of ectopic endometrial tissue were significantly decreased. The relative expression area of Bad in ectopic endometrial tissue was significantly increased, the relative expression area of Bcl-2 was significantly decreased, and the apoptosis rate was significantly elevated as shown by TUNEL staining. Serum levels of IL-1β, IL-6, TNF-α, EGF, and EGFR were significantly reduced, and the relative protein expression levels of EGFR, PI3K, p-PI3K, Akt, and p-Akt, as well as the mRNA expression levels of EGFR, PI3K, and Akt, were significantly decreased (P<0.05,P<0.01). ConclusionModified Shaofu Zhuyutang may exert therapeutic effects on endometriosis by interfering with key proteins of the EGFR/PI3K/Akt signaling pathway and inducing apoptosis in ectopic endometrial tissue.
6.Effect of Modified Shaofu Zhuyutang on Ferroptosis in Ectopic Endometrial Tissues of Rats with Endometriosis Based on MDM4/p53/GPX4 Signaling Pathway
Zuoliang ZHANG ; Xiangyu LIN ; Wanrun WANG ; Jiaxing WANG ; Yaling YANG ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):39-47
ObjectiveTo investigate the mechanism of modified Shaofu Zhuyutang in inducing ferroptosis in ectopic endometrial tissues of rats with endometriosis through the murine double minute 4 (MDM4)/tumor suppressor p53/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsSeventy SPF-grade female SD rats were randomly divided into a blank group (n = 10), a sham-operated group (n = 10), and a modeling group (n = 50). The sham-operated group underwent laparotomy, while the modeling group was subjected to the autotransplantation method to establish an endometriosis model. After successful modeling, the animals were randomly assigned to the model group, progesterone group (0.25 mg·kg-1), and modified Shaofu Zhuyutang high-, medium-, and low-dose groups (30, 15, and 7.5 g·kg-1, respectively), with 10 rats per group. After four weeks of drug administration, the rats were euthanized for sample collection. The weight and volume of ectopic endometrial tissues were recorded for each group. Transmission electron microscopy (TEM) was employed to observe ultrastructural changes in endometrial tissues, while Prussian blue staining was used to assess iron ion deposition. Serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The relative levels of Fe2+, malondialdehyde (MDA), and glutathione (GSH) in endometrial tissues were determined by colorimetric assay. Immunofluorescence (IF) was used to detect the relative fluorescence intensities of GSH and GPX4 in endometrial tissues. The relative expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), MDM4, p53, and GPX4 proteins were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, MDM4, p53, and GPX4. ResultsCompared with the blank and sham-operated groups, the model group exhibited reduced ferroptotic damage in ultrastructural observations, decreased ferroptotic aggregates and positive iron ion expression area on Prussian blue staining, elevated serum IL-6, IL-1β, and TNF-α levels, reduced Fe2+ and MDA content, increased GSH content in endometrial tissues, and enhanced GSH and GPX4 fluorescence intensities (P<0.01). The protein and mRNA expression levels of PI3K, p-PI3K, Akt, p-Akt, MDM4, and GPX4 were elevated, while those of p53 were decreased (P<0.01). Compared with the model group, in the progesterone group and the modified Shaofu Zhuyutang high- and medium-dose groups, ferroptotic damage in ultrastructural observations was exacerbated to varying degrees by TEM, and ferroptotic aggregates and positive iron ion expression areas were increased on Prussian blue staining. Serum IL-6, IL-1β, and TNF-α levels decreased, Fe2+ and MDA content increased, and GSH content decreased in endometrial tissues. GSH and GPX4 fluorescence intensities weakened, while the protein and mRNA expression levels of PI3K, p-PI3K, Akt, p-Akt, MDM4, and GPX4 decreased, and those of p53 increased (P<0.05, P<0.01). Conclusionmodified Shaofu Zhuyutang may exert therapeutic effects in endometriosis by inducing ferroptosis in ectopic endometrial tissues, alleviating inflammatory responses, and modulating key proteins in the MDM4/p53/GPX4 signaling pathway.
7.Huoluo Xiaolingdan Suppresses Triple-negative Breast Cancer in Mice by Regulating TCF1+ CD8+ Stem Cell-like T Cells Infiltration
Bo LUO ; Qu ZHANG ; Yujie SUN ; Lin LIU ; Lan ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):108-115
ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer (TNBC) in mice through its regulation of TCF1+CD8+ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group, low-dose (3.9 g·kg-1), medium-dose (7.8 g·kg-1) and high-dose (15.6 g·kg-1) Huoluo Xiaolingdan groups, and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g-1, while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group, mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week, for a total of five injections. The tumor volume, survival time and tumor mass were measured at different time points. Hematoxylin-eosin (HE) staining was used to observe the histological changes of the tumor. The expression of CD8+T cells and TCF1+CD8+ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1+CD8+ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group, the tumor volume and mass of in low-, medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased (P<0.05, P<0.01). The median survival time of mice in low-, medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows: 27.00 days (95%CI, 0.45-2.65), 31.00 days (95%CI, 0.32-1.89), 34.00 days (95%CI, 0.40-2.33), and 35.00 days (95%CI, 0.42-2.47). All of them were higher than that of the model group [24.50 days (95%CI, 0.37-10.5)]. Flow cytometry showed that compared with the model group, the proportion and number of infiltrating CD8+ T cells in tumor were increased in low-, medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group (P<0.05, P<0.01), while the proportion of tumor regulatory T cells (Treg) and M2 macrophages decreased (P<0.05). Compared with the model group, the proportion of IFN-γ+CD8+ T and GrzB+CD8+ T cells in tumors in low-, medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased (P<0.01), and the proportion of TCF1+CD8+ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1+CD8+ T cells in tumor tissues increased in low-, medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1+CD8+ stem-like T cells, enhancing CD8+ T cell activity, and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.
8.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
9.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
10.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

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