1.Progress of Anti-osteoporosis Research of Traditional Chinese Medicine Based on Zebrafish Model
Henghong WANG ; Xinyu FAN ; Yihan GAO ; Zhilue LUO ; Peng DUAN ; Yunfeng ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):323-330
Osteoporosis (OP) is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast, traditional Chinese medicine has a long history and a rich species diversity. Furthermore, recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish, due to its favourable optical transparency and high homology with human genes, has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies, an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model, and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed, as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore, the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases, as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.
2.Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand.
Xin ZHOU ; Jiahui CHEN ; Jimmy S PATEL ; Wenqing RAN ; Yinlong LI ; Richard S VAN ; Mostafa M H IBRAHIM ; Chunyu ZHAO ; Yabiao GAO ; Jian RONG ; Ahmad F CHAUDHARY ; Guocong LI ; Junqi HU ; April T DAVENPORT ; James B DAUNAIS ; Yihan SHAO ; Chongzhao RAN ; Thomas L COLLIER ; Achi HAIDER ; David M SCHUSTER ; Allan I LEVEY ; Lu WANG ; Gabriel CORFAS ; Steven H LIANG
Acta Pharmaceutica Sinica B 2025;15(10):5036-5049
Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its 18F-isotopologue ([18F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [18F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [18F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.
3.A flavin-containing monooxygenase from Schizosaccharomyces pombe: characterization and application in the synthesis of S-methyl-L-cysteine sulfoxide.
Mengka LIAN ; Zhaolin SONG ; Wenjing GAO ; Gang ZHU ; Mengjun DONG ; Yu LI ; Yihan LIU ; Fenghua WANG ; Fuping LU
Chinese Journal of Biotechnology 2025;41(1):474-485
S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg2+ improved the enzyme activity. The enzyme kinetic analysis showed that the Km and kcat/Km of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics*
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Escherichia coli/metabolism*
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Recombinant Proteins/metabolism*
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Cysteine/biosynthesis*
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Mixed Function Oxygenases/metabolism*
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Schizosaccharomyces pombe Proteins/metabolism*
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Oxygenases/metabolism*
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Kinetics
4.A case of type 1 diabetes caused by gastric cancer treated with Sintilimab
Yihan GAO ; Jingyu CHEN ; Haoyu FU ; Junquan YANG
Clinical Medicine of China 2024;40(1):70-72
Immune checkpoint inhibitors (ICIs) are currently used in the treatment of various tumors and play an important role in tumor treatment, resulting in many adverse reactions related to the immune system. Type 1 diabetes (T1DM) is a rare endocrine system complication, which is rarely reported at present. We report a case of T1DM after using ICIs to treat gastric cancer. The patient was a 34 year old male who developed diabetes ketoacidosis after 206 days of sintilimab monoclonal antibody use, with fasting blood glucose of 15.78 mmol/L and glycosylated hemoglobin of 8.6%. Islet related antibody: Glutamate decarboxylase antibody: 119.2 IU/mL; Insulin antibody:<2 IU/L. Fasting insulin: 0.21 mU/L; Fasting C-peptide: 0.12 μg/L. Through the analysis of patients' clinical data, it aims to improve clinicians' understanding of immune related type 1 diabetes and provide ideas for correct diagnosis and treatment.
5.Analysis of the Nature,Flavor and Combination Characteristics of the Two-herb Compound Formulas inTreatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》)
Ying ZHANG ; Yihan ZHAO ; Qinghua SHANG ; Ruina BAI ; Wenhui DUAN ; Jianpeng DU ; Zhuye GAO ; Zhonghui JIANG ; Dazhuo SHI
Journal of Traditional Chinese Medicine 2024;65(22):2378-2382
Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica (《神农本草经》); Miscellaneous Records of Famous Physicians (《名医别录》), this study analyzed the characte-ristics of the natures, flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》).Finally, 31 compound formulas were included, and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas, such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi, the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat, the sweet and the bitter in pairs to remove dampness and clear heat, the acrid and the acrid in pairs to arrest vomiting and direct qi downward, and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease, the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors, with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.
6.Glycyrrhizic acid-based multifunctional nanoplatform for tumor microenvironment regulation.
Meng XIAO ; Zhiqing GUO ; Yating YANG ; Chuan HU ; Qian CHENG ; Chen ZHANG ; Yihan WU ; Yanfen CHENG ; Wui Lau Man BENSON ; Sheung Mei Ng SHAMAY ; George Pak-Heng LEUNG ; Jingjing LI ; Huile GAO ; Jinming ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(12):1089-1099
Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals
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Humans
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Antineoplastic Agents/therapeutic use*
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Glycyrrhizic Acid/therapeutic use*
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Liposomes/chemistry*
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Micelles
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Nanoparticles/chemistry*
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Neoplasms/pathology*
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Tumor Microenvironment/drug effects*
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Nanoparticle Drug Delivery System/therapeutic use*
7.Distribution of age at onset and its influence on clinical characteristics of 164 patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome
Cui GAO ; Yihan CAO ; Chen LI ; Xia WU ; Jinhe LIU ; Weixin HAO ; Wen ZHANG ; Zhenhua DONG
Chinese Journal of Rheumatology 2018;22(2):82-86
Objective To investigate the distribution of age at onset and its influence on clinical characteristics in synovitis,acne,pustulosis,hyperostosis,and osteitis (SAPHO) syndrome.Methods We recruited 164 patients with SAPHO syndrome who presented to Peking Union Medical College Hospital from Jan 2004 to Mar 2015.All the patients were assessed for medical history,laboratory tests and imaging presentations.The distribution of age at onset was analyzed using Shapiro-Wilknormality test and Kolmogorov-Smimov test for mixed normal distribution.The influence of age at onset on clinical features was analyzed using Mann-Whitney U test and x2 test.Results A double-peak mixed normal distribution of age at onset of skin lesions was found in female patients with SAPHO syndrome,with means and standard deviations of (30±6) years (early-onset) and (51 ±7) years (late-onset) for each mixed normal distribution.The cut-off point was determined to be 42 years old.Nonetheless,a typical single-peak normal distribution of age at onset of skin lesions was observed in male patients.A significantly higher frequency of thoracic region pain [14/36 (38.9%) vs 6/70 (8.6%),x2=14.28,P<0.01,spinal lesions revealed by bone scintigraphy [23/35 (65.7%) vs 23/66(34.8%),x2=8.79,P=0.003],and peripheral skeletal lesions revealed by bone scintigraphy [17/35 (48.6%) vs 17/66(25.8%),x2=5.33,P=0.021] were found in late-onset female patients compared with early-onset ones.Moreover,female patients with late onset had significantly higher hs-CRP level [(12±12) mg/L vs (9±11) mg/L;U=911.5,P=-0.042)],pain VAS (4.8±1.8 vs 4.0±2.1;U=948,P=0.036),and BASFI (3.0±2.2 vs 1.8±2.0;U=822.5,P=0.003) at baseline than those with early onset.Conclusion Female patients with SAPHO syndrome have a double-peak distribution of age at onset of skin lesions.Female patients with early and late onset of skin lesions exhibit distinct clinical characteristics.
8. Review on methods in the disease burden assessment attributable to household air pollution
Xuehuan GAO ; Renjie CHEN ; Haidong KAN ; Wei LIU ; Furong DENG ; Jingguang LI ; Yinping ZHANG ; Yihan LU ; Zhuohui ZHAO
Chinese Journal of Preventive Medicine 2018;52(12):1315-1320
In the past decades, people's work and life styles have dramatically changed during the rapid economic development and urbanization in China. A national survey reported that Chinese adults spend an average of 81% of daily time in indoor environment. Exposure to indoor air pollution plays key roles for human health but is likely to be neglected due on the relatively lower concentration levels and lower awareness among common people. Till now, published studies focus more on the pollution levels or the toxicological effects of indoor air pollutants but there is a lack of disease burden assessment attributable to indoor air pollution. In this review, several international studies were introduced on the disease burden estimation attributable to indoor air pollution, as well as the estimation methods. The current situation of national study was also reviewed. The strengths and limitations of the representative international studies were discussed. This review is helpful in providing data to guide the research on disease burden assessment attributable to indoor air pollution in China, and further helps to prioritize the indoor air pollution control based on disease burden ranking among pollutants and motivate public policies to protect the public health.
9.In vitro release and antibacterial property of minocycline-hydroxyapatite/chitosan complex
Haochen GAO ; Pei WANG ; Zhizhong CAO ; Kuikui GE ; Yihan WANG ; Min LU
Chinese Journal of Tissue Engineering Research 2016;20(8):1118-1125
BACKGROUND: Hydroxyapatite/chitosan (HA/CS) complex may act as a drug carrier for drug release, but little is reported about the release amount and antibacterial effect of minocycline-HA/CS (Mino-HA/CS) complex. OBJECTIVE: To investigate the in vitro release and antibacterial property of Mino-HA/CS complex. METHODS: HA/CS and Mino-HA/CS were prepared using co-precipitation method. The surface and cross-section features of the complexes were observed under scanning electron microscopy. The porosities were measured according to Archimedes Principle. The release of minocycline hydrochloride was measured by high performance liquid chromatography with the simulated saliva as drug release media. In vitro antibacterial effect on Porphyromonas gingivalis and Staphylococcus aureus were measured by bacteria-inhibiting ring method. Biological toxicities were evaluated via cel counting kit-8cel proliferation assay. RESULTS AND CONCLUSION: The porosity of Mino-HA/CS was larger than that of HA/CS, with the average porosity of 53.99%. Single-day release amount of Mino-HA/CS could maintain at the level of 0.5-1 μg per day for a long-term. Bacteriostatic rings of Porphyromonas gingivalis and Staphylococcus aureus stil existed clearly after 7 days. Cel proliferation assays showed that Mino-HA/CS extract had the significant effect on promoting cel proliferation. These findings indicate that the Mino-HA/CS sustains the release of minocycline at a relatively stable level within a longer period, shows good inhibitory effect on Porphyromonas gingivalis and Staphylococcus aureus and promotes the proliferation of periodontal ligament cel s.
10.Effects of full Marathon on striated muscle and renal function of Marathon amateurs without complaints
Hao XU ; Yan WEN ; Lili ZHAO ; Jing CHEN ; Guiyang LU ; Yihan HOU ; Liufang GAO ; Minwei ZHANG
Chinese Critical Care Medicine 2016;28(10):933-936
Objective To approach the effects of full Marathon on striated muscle and renal function of Marathon amateurs without complaints. Methods A prospective self-paired design study was conducted. The amateurs without body discomfort, hematuria, brown urine, or persistent muscle pain within 1 week after the 2012 Xiamen International Marathon Race were enrolled voluntarily. The peripheral blood and random urine specimens of all subjects under static status 1 week before the race and after the race instantly (within 10 minutes after finishing the race) were collected to detect markers of renal function and striated muscle injury. Results Sixty-one subjects were included in the final analysis of the study with full Marathon of 42.195 km and mean race time of (297.05± 55.60) minutes. Compared with those under static status before the race, the markers of renal function including the levels of urinary N-acetyl-beta-D-glucusamidase [NAG (U/L): 64.00 (54.50, 85.50) vs. 9.50 (8.10, 11.50)], urinary β2-microspheres protein [β2-MG (μg/L): 261.00 (128.50, 1 608.00) vs. 66.60 (33.75, 123.00)], random urinary creatinine [UCr (μmol/L): 19 066.56±10 938.31 vs. 5 872.52±4 363.20] and serum creatinine [SCr (μmol/L): 129.97±25.84 vs. 97.39±14.51] immediately after the race were significantly increased (all P < 0.01); the markers of muscle injury including the levels of serum creatine kinase [CK (U/L): 864.00 (504.00, 1 644.00) vs. 164.00 (128.00, 256.00)], lactic dehydrogenase [LDH (U/L): 383.26±141.69 vs. 182.23±41.12], myoglobin [Mb (mg/L): 1 880.00 (1 080.00, 3 300.00) vs. 42.00 (36.00, 54.50)], alanine aminotransferase [ALT (U/L): 27.0 (19.5, 38.0) vs. 24.0 (15.0, 29.5)] and aspartate transaminase [AST (U/L): 52.07±25.13 vs. 28.28±11.86] were also significantly increased (all P < 0.01), and the increase in CK, Mb, and LDH were more significant. It was shown by correlation analysis that CK after race was negatively correlated with age (r = -0.352, P = 0.005) and body mass index (r = -0.271, P = 0.035), and it was positively correlated with racing time (r = 0.387, P = 0.002) and urinary β2-MG after the race instantly (r = 0.364, P = 0.004). Mb after race was negatively correlated with body mass index (r = -0.331, P = 0.009), and it was positively correlated with urinary β2-MG after the race instantly (r = 0.315, P = 0.013). LDH after race was negatively correlated with age (r = -0.275, P = 0.032) and body mass index (r = -0.377, P = 0.003), and it was positively correlated with urinary β2-MG after the race instantly (r = 0.424, P = 0.001). Conclusion Full Marathon could significantly impact striated muscle and renal function of Marathon amateurs without complaints.

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