1.THBS4 in Disease: Mechanisms, Biomarkers, and Therapeutic Opportunities
De-Ying HUANG ; Yan-Hong LI ; Xiu-Feng BAI ; Yi LIU
Progress in Biochemistry and Biophysics 2025;52(9):2217-2232
Thrombospondin 4 (THBS4; TSP4), a crucial component of the extracellular matrix (ECM), serves as an important regulator of tissue homeostasis and various pathophysiological processes. As a member of the evolutionarily conserved thrombospondin family, THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions. Through dynamic interactions with various ECM components, THBS4 plays pivotal roles in cell adhesion, proliferation, inflammation regulation, and tissue remodeling, establishing it as a key modulator of microenvironmental organization. The transcription and translation of THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4 research(1) the fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.
2.Effects and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats
Dong AN ; Yong-Lin LIANG ; Yan-Kui GAO ; Feng-Zhe YAN ; Min BAI ; Si-Chen ZHAO ; Zhong-Tang LIU ; Xiao NIE
The Chinese Journal of Clinical Pharmacology 2024;40(9):1282-1286
Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.01,P<0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.
3.Research progress in regulation and mechanism of transcription factors on tanshinones
Yan-hong BAI ; Lin-lin XIN ; Ting ZENG ; Feng-xia HAN ; Yong-qing ZHANG ; Gao-bin PU ; Xue CHEN ; Qian LIU
Acta Pharmaceutica Sinica 2024;59(5):1218-1228
italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of
4.Two new flavonoid glycosides from Diphylleia sinensi
Hao-jie WANG ; Chen ZHAO ; Yan-jun SUN ; Jian-hong GONG ; Hong-yun BAI ; Hui CHEN ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2024;59(3):673-677
Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of
5.A Precise and Portable Detection System for Infectious Pathogens Based on CRISPR/Cas Technology
Yi-Chen LIU ; Ru-Jian ZHAO ; Bai-Yang LYU ; De-Feng SONG ; Yi-Dan TANG ; Yan-Fang JIANG ; Bing-Ling LI
Chinese Journal of Analytical Chemistry 2024;52(2):187-197
Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.
6.Discussion on Differentiation and Treatment of Sudden Hearing Loss by Traditional Chinese Medicine Based on the Classification of Hearing Curve
Xinru WANG ; Yang LI ; Jiajia ZHANG ; Yan MENG ; Chongyang ZHANG ; Xueshi DI ; Zhiwei FENG ; Junjie LIANG ; Peng BAI
Journal of Traditional Chinese Medicine 2024;65(11):1126-1131
Pure-tone audiometry can be performed to evaluate the type and degree of hearing loss, whose results can be divided into four types including low-frequency descending, high-frequency descending, flat descending and total deafness. The low-frequency descending type of sudden hearing loss (SHL) is more likely to be spleen deficiency and dampness exuberance, the high-frequency descending type is often due to yin deficiency of liver and kidney, the flat descending type is commonly associated with qi and blood depletion, and the type of total deafness is often linked to blood stasis. Our team has further developed a comprehensive diagnostic and therapeutic approach for SHL, emphasizing "the integration of disease and syndrome, the combination of acupuncture and herbal medicine, and dynamically administering treatment". Firstly, it advocates integrating disease diagnosis with syndrome differentiation. Secondly, it recommends combining acupuncture and herbal medicine, with local acupoints such as Ermen (TE 21), Tinggong (SI 19), Tinghui (GB 2), and Yifeng (TE 17) used to unblock the auditory orifice, and herbal prescriptions tailored to the hearing curve patterns. For the low-frequency descending type, it is recommended to fortify the spleen and percolate dampness by taking distal points of spleen channel and stomach channel and using Shenling Baizhu Powder (参苓白术散). For the high-frequency descending type, the method of nourishing kidney and calming liver is recommended, using distal points of kidney and liver channels and taking Erlong Zuoci Pills (耳聋左慈丸). Regarding the flat descending type, tonifying qi and nourishing blood is advised, for which acupoints of Conception Vessel, spleen, stomach and large intestine channels can be needled, and Yiqi Congming Decoction (益气聪明汤) can be administered. For the total deafness type, it is recommended to activate blood and dissipate stasis, often with Xuehai (SP 10) and Geshu (BL 17) needled and Tongqiao Huoxue Decoction (通窍活血汤) administered. All these are conducted to treat the root and branch simultaneously. At the same time, it emphasizes the need to consider complex syndrome presentations and disease progression, dynamically analyze the disease causes and mechanisms, and adjust treatment according to the changing syndromes. In conclusion, this article is expected to inspire clinical diagnosis and treatment of SHL.
7.Chemical constituents from stems and leaves of Lonicera confusa and their anti-inflammatory activities
Xiao-Hua JIANG ; Yu-Lu WEI ; Jun BAI ; Xiao-Jie YAN ; Dian-Peng LI ; Feng-Lai LU
Chinese Traditional Patent Medicine 2024;46(2):484-489
AIM To study the chemical constituents and their anti-inflammatory activities of stems and leaves of Lonicera confusa DC.METHODS The 80%methanol extract from stems and leaves of L.confusa DC was isolated and purified by Diaion HP20SS,Sephadex LH-20,HSCCC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by measuring NO production of LPS-stimulated RAW264.7 cells in vitro.RESULTS Thirteen compounds were isolated and identified as benzyl alcohol-O-β-D-glucopyranosyl-(1 →6)-β-D-glucopyranoside(1),sweroside(2),epi-vogeloside(3),vogeloside(4),secologanoside(5),secoxyloganin(6),secologanin dimethyl acetal(7),methyl chlorogenate(8),apigenin-7-O-β-D-glucopyranoside(9),luteolin-7-O-β-D-glucopyranoside(10),rhoifolin(11),luteolin-7-O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(12),and lonicerin(13).Compounds 2-8,11-13 inhibited the NO production of LPS-induced cells.CONCLUSION Compound 1 is first isolated from family Lonicera,compounds 3,5,7,9,11,and 12 are obtained from the stems and leaves of this plant for the first time.Compounds 2-8,11-13 exhibited anti-inflammatory activities.
8.Effects of three sterilization methods on the magnetic flux of magnetic surgical devices and analysis of sterilization cost
Feng MA ; Aihua SHI ; Xiaoyan ZENG ; Fang BAI ; Ningxia JIA ; Hao XUE ; Fengling WANG ; Yan LI ; Xufeng ZHANG ; Yi LÜ ; Lingling SHI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):669-673
Objective To analyze the effects of three sterilization methods,namely,pressure steam,low-temperature plasma and ethylene oxide,on the magnetic flux of magnetic surgical devices and their sterilization costs.Methods A total of 234 magnetic surgical devices of different specifications and models(magnetic rings)were randomly divided into Group A,Group B and Group C after the paired number was labelled,and each group consisted of 78 pieces(39 pairs).After packaging each pair of devices according to sterilization specifications,Group A was sterilized by pressure steam,Group B was sterilized by low-temperature plasma,and Group C was sterilized by ethylene oxide.We measured the magnetic flux of three sets of magnetic rings before and after sterilization,and comparatively analyzed the sterilization cost and sterilization time of the single package.Results There was no statistically significant difference in the impact of the three sterilization methods on the magnetic flux of the magnetic surgical devices(P>0.05),but there was a significant difference in the magnetic flux before and after sterilization for each sterilization method(P<0.001);the sterilization cost was(1.96±0.16)yuan for Group A,(23.17±0.32)yuan for Group B,and(8.16±0.18)yuan for Group C,showing statistically significant differences among the three groups(P<0.01).The sterilization time was(65.21±3.36)min for Group A,(45.46±1.39)min for Group B,and(1020.38±12.21)min for Group C,with statistically significant differences among the three groups(P<0.01).Conclusion None of the three sterilization methods affects the magnetic flux of the magnetic surgical devices.Pressure steam method shows the lowest cost of single package,low-temperature plasma method shows the highest cost of single package,while ethylene oxide method shows the highest sterilization time.Pressure steam should be the preferred sterilization method for magnetic surgical devices.
9.A case of oral chloropicrin poisoning
Jinyue FENG ; Shixian BAI ; Xiuwen ZHANG ; Chao YAN ; Peng CHENG ; Yutian ZHUANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(8):627-629
Chloropicrin is a commonly used pesticide in agricultural production. The clinical manifestations of oral poisoning patients are complex, and the lesions involve multiple organs. At present, the specific pathogenic mechanism of such poisoning is not clear, and the treatment experience is insufficient, so there are certain difficulties in clinical diagnosis, treatment and treatment. In this paper, the data of a patient with oral chloropicrin poisoning treated in Yidu Central Hospital of Weifang City in April 2023 were summarized. The patient was admitted to our hospital for treatment in time, and his condition improved after Hemopurification, methylene blue reduction, organ support, infection prevention as well as other symptomatic support. Oral chlorophenol can cause lung damage, skin and mucous membrane damage, and may have certain effects on the nervous system and kidney. Early intervention, especially blood purification, is effective.
10.A case of oral chloropicrin poisoning
Jinyue FENG ; Shixian BAI ; Xiuwen ZHANG ; Chao YAN ; Peng CHENG ; Yutian ZHUANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(8):627-629
Chloropicrin is a commonly used pesticide in agricultural production. The clinical manifestations of oral poisoning patients are complex, and the lesions involve multiple organs. At present, the specific pathogenic mechanism of such poisoning is not clear, and the treatment experience is insufficient, so there are certain difficulties in clinical diagnosis, treatment and treatment. In this paper, the data of a patient with oral chloropicrin poisoning treated in Yidu Central Hospital of Weifang City in April 2023 were summarized. The patient was admitted to our hospital for treatment in time, and his condition improved after Hemopurification, methylene blue reduction, organ support, infection prevention as well as other symptomatic support. Oral chlorophenol can cause lung damage, skin and mucous membrane damage, and may have certain effects on the nervous system and kidney. Early intervention, especially blood purification, is effective.

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