1.Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling.
Yong RAO ; Rui SU ; Chenyan WU ; Xingxing CHAI ; Jinjian LI ; Guanyu YANG ; Junjie WU ; Tingting FU ; Zhongping JIANG ; Zhikai GUO ; Congjun XU ; Ling HUANG
Acta Pharmaceutica Sinica B 2024;14(1):304-318
Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.
2.Clinical analysis of aortographic manifestations in 30 child patients with Kawasaki disease
Jia FU ; Yong ZHANG ; Jing LIU ; Yong YANG ; Aiguo ZHAI ; Juanjuan DING
Journal of Interventional Radiology 2024;33(2):126-129
Objective To summarize the aortographic features of child patients with Kawasaki disease(KD)complicated by coronary artery lesion(CAL)who were treated at the Wuhan Children's Hospital of China.Methods The clinical data of 30 child patients with early recovery stage KD complicated by CAL,who received aortic angiography examination at Wuhan Children's Hospital of China between June 2016 and June 2023,were retrospectively analyzed.Preoperative echocardiography was adopted to evaluate the severity of CAL,and aortic angiography under laryngeal mask general anesthesia was performed.Results Successful aortic angiography examination was accomplished in all the 30 child patients with KD complicated by CAL.After angiography,the CAL risk classification results showed that grade I was seen in 5,grade Ⅱ in 7,grade Ⅲ in 12,grade Ⅲ in 4,and grade V in 2 child patients.Of all child patients,old coronary thrombosis was found in one(grade Ⅲb),and coronary artery stenosis with collateral circulation formation in one(grade Ⅴ).The CAL was located at the proximal segment(n=15),middle segment(n=3)and distal segment(n=2)of the right coronary artery,at the left main coronary artery(n=12),and at the proximal segment of left coronary artery anterior descending branch(n=9).Electrocardiography showed sinus rhythm(n=17),sinus arrhythmia(n=4),right bundle branch block(n=4),atrial premature beat(n=1),ventricular premature beat(n=2),T-wave change(n=1),and Q-wave change(n=1,coronary lesion grade V,echocardiography suggested left heart enlargement).No cardiac enlargement,cardiac functional insufficiency,or valvular regurgitation signs were observed in the remaining child patients.Conclusion It is clinically safe and feasible to perform aortic angiography examination in child patients with early recovery stage KD complicated by CAL.In this series of child patients with KD,CAL mainly occurs at the proximal segment of coronary artery,especially at the proximal segment of right coronary artery as well as at the left main artery and left anterior descending branch.
3.Research status on the mechanism of traditional Chinese medicine regulating TGF-β1/Smads signaling pathway to intervene liver fibrosis
Yong-Biao TAO ; Shi-Rui YANG ; Long-De WANG ; Ya-Na WU ; Zhi-Ming ZHANG ; Fu LI
The Chinese Journal of Clinical Pharmacology 2024;40(6):918-922
Hepatic fibrosis(HF)is a pathophysiological outcome of chronic liver injury and is characterized by excessive accumulation of extracellular matrix protein.A number of studies have confirmed that the signaling pathways formed by transforming growth factor-β1(TGF-β1)and its downstream Smad family play an important role in the occurrence and development of HF,and the traditional Chinese medicine(TCM)research targeting this pathway is currently a hot spot in the reversal of HF.Therefore,taking TGF-β1/Smads signaling pathway as the entry point,this paper reviewed the mechanism of action of TCM compound formula and single drug extract in intervening TGF-β1/Smad pathway and related factors upstream and downstream of the pathway to reverse HF in recent years,revealed the targeted therapeutic effect of TCM,and provided new strategies for clarifying the mechanism of TCM.
4.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
5.IL2rg-/- rats support prolonged infection of human RSV
Rui XIONG ; Yong WU ; Yanwei YANG ; Zhe QU ; Susu LIU ; Yuya WANG ; Liying MA ; Rui FU ; Yihong PENG ; Chunnan LIANG ; Changfa FAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):17-24
Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0~35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.
6.Establishment and evaluation methods of a novel animal model of liver depression transforming into fire syndrome-related depression
Dan SU ; Jian LI ; Gen-hua ZHU ; Ming YANG ; Liang-liang LIAO ; Zhi-fu AI ; Hui-zhen LI ; Ya-li LIU ; Yong-gui SONG
Acta Pharmaceutica Sinica 2024;59(6):1680-1690
Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and
7.Evaluation of performance of disposable medical protective clothing for resistance to infective agent penetration
Ke-Yang LIU ; Yan FENG ; Juan ZHANG ; Yue NIU ; Dan QIN ; Yong-Fu HUANG ; Guang-Yong HU
Chinese Medical Equipment Journal 2024;45(5):16-21
Objective To evaluate the performance of the disposable medical protective clothing in blocking the penetration of infectious agents,in order to provide data support for the setting of such performance indexes when the GB 19082 is revised.Methods Totally 10 batches of different brands and models of protective clothing were selected,and tests were carried out for penetration resistance to synthetic blood,phage,wet microorganisms,dry microorganisms and contaminated liquid aerosol and particle filtration efficiency according to YY/T 0700-2008,YY/T 0689-2008,YY/T 0506.6-2009,GB 19082-2009,YY/T 0506.5-2009 and YY/T 1799-2020.Results There were 2 batches of protective clothing with anti-synthetic blood penetration performance level 2,3,4,5 and 6,respectively;all the protective clothing had the highest level 6 for anti-wet microorganisms penetration,part of whom had the levels for the resistance to phage penetration lower than those for preventing anti-synthetic blood penetration;all of the protective clothing had the particle filtration efficiencies higher than 95%,and had the highest level 3 for anti-dry microorganisms penetration;there're 5 batches of protective clothing with the highest level 3 for contaminated liquid aerosol penetration,1 batch with level 2 and the remained 4 batches with undetermined levels,which all had an average logarithmic reduction higher than 4.5 after penetration.Conclusion Particle filtration efficiency and resistance to phage penetration may be involved in the requirements for resistance to infective agent penetration in revised GB 19082 for evaluating the ability of protective clothing materials to block microorganisms in airborne particles and liquid contaminants.[Chinese Medical Equipment Journal,2024,45(5):16-21]
8.Interpretation of YY 1881-2023 Powered air-purifying respirator(PAPR)used in healthcare settings
Ke-Yang LIU ; Yong-Fu HUANG ; Guang-Yong HU
Chinese Medical Equipment Journal 2024;45(8):1-6
The standard YY 1881-2023 Powered air-purifying respirator(PAPR)used in healthcare settings was introduced in terms of development background,foreign and China's standards involved in during its development and settings of related product performance indicators,which was interpreted from the aspects of scope of application,classificantion and marking of targeted products and main performance requirements.References were provided for correct understanding of the standard terms and product development,manufacturing,inspection and etc.[Chinese Medical Equipment Journal,2024,45(8):1-6]
9.Interpretation of YY 1887-2023 Positive pressure protective clothing(PPPC)for medical use
Ke-Yang LIU ; Yong-Fu HUANG ; Guang-Yong HU
Chinese Medical Equipment Journal 2024;45(8):7-11
The standard YY 1887-2023 Positive pressure protective clothing(PPPC)for medical use was introduced in terms of development background and foreign and China's standards involved in during the standard development,which was interpreted from the aspects of scope of application,structural composition and main performancerequirements.References were provided for correct understanding of the standard terms and product development,manufacturing,inspection and etc.[Chinese Medical Equipment Journal,2024,45(8):7-11]
10.Interpretation of YY 1885-2023 Negative pressure isolators for transport of infectious patients
Ke-Yang LIU ; Yong-Fu HUANG ; Guang-Yong HU
Chinese Medical Equipment Journal 2024;45(8):12-15
The standard YY 1885-2023 Negative pressure isolators fortransport of infeectious patients was introduced in terms of development background,which was interpreted from the aspects of definition of terms,scope of application and performance requirements.References were provided for correct understanding of the standard terms and product development,manufac-turing,inspection and etc.[Chinese Medical Equipment Journal,2024,45(8):12-15]

Result Analysis
Print
Save
E-mail