1.Current drug research on intestinal mucosal healing in inflammatory bowel disease based on macrophage regulation
Xin-ke DU ; Qing-sen RAN ; Li LIU ; Qing YANG ; Li-dong SUN ; Yu-jie LI ; Ying CHEN ; Xiao-xin ZHU ; Qi LI
Acta Pharmaceutica Sinica 2021;56(12):3392-3400
Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.
2.Microvascular study of the transmidline scapular flap vascularized by the contralateral circumflex scapular artery.
Ran HUO ; Sen-Kai LI ; Yang-Qun LI ; Qiang LI ; Ming-Yong YANG ; Wei-Qing HUANG ; Yuan-Bo LIU
Chinese Journal of Plastic Surgery 2004;20(4):262-264
OBJECTIVETo observe the microvascular distribution of the transmidline scapular flap supplied by the contralateral circumflex scapular artery.
METHODSThe integument and deep tissues of 6 fresh cadavers were dissected and radiographed after vermilion mixture was injected to the unilateral circumflex scapular artery.
RESULTSThe vascular tree passed the midline and reached to the contralateral acromion. The vessel density was the highest in the irrigating side of the back, which was higher in the middle area. In the contralateral side,the high vessel density concentrated in the upper part of the back.
CONCLUSIONSThe result revealed the direct evidence for the clinical application of the transmidline scapular flap. In design and elevating of the transmidline scapular flap, it should be slanting to the upper part of the contralateral back.
Arteries ; anatomy & histology ; Cadaver ; Diagnostic Imaging ; methods ; Female ; Humans ; Male ; Scapula ; transplantation ; Surgical Flaps ; blood supply
3.Hemodynamic study of an over-midline axial flap.
Ran HUO ; Sen-kai LI ; Yang-qun LI ; Qiang LI ; Ming-yong YANG ; Wei-qing HUANG
Chinese Journal of Plastic Surgery 2004;20(3):171-173
OBJECTIVETo investigate the hemodynamic changes of an over-midline axial flap.
METHODSAn over-midline axial flap, based on the iliac artery and veins, was raised on the back of each selected Wistar rat (n = 30), vascularied by contralateral. The flap size is 7 cm x 3 cm. The over-midline part is 3 cm x 3 cm. A laser doppler flowmetry (LDF) was used to evaluate the hemodynamic changes preoperatively, and 6 hours, 24 hours, 48 hours, 72 hours, 7 days, and 14 days after the operation respectively.
RESULTSAll of the flaps survived well. But, in the first three days after the operation, the blood perfusion of the flap in the areas of the midline and the distal part was significantly lower than the preoperation's level. Thereafter, the values of the blood perfusion started to increase till to the maximum 7 days after the operation. On the 14 days after the operation, the vascular structures was axially matched to the base of the flap. In the distal part of the flap, the choke vessels were gradually opened and resulted in the blood perfusion to the normal level.
CONCLUSIONThe hemodynamic changes of the over-midline axial flap transmidline flap could occur to match the need of the base of the flap.
Animals ; Female ; Hemodynamics ; physiology ; Male ; Models, Animal ; Rats ; Rats, Wistar ; Surgical Flaps ; blood supply ; Time Factors
4.Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory
Li-na YANG ; Xin-ke DU ; Li LIU ; Man-jing LI ; Qing-sen RAN ; Qing YANG ; Li-dong SUN ; Yu-jie LI ; Ying CHEN ; Xiao-xin ZHU ; Qi LI
Acta Pharmaceutica Sinica 2022;57(6):1593-1603
The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.
5.Wide Pulse Width Electroacupuncture Ameliorates Denervation-Induced Skeletal Muscle Atrophy in Rats via IGF-1/PI3K/Akt Pathway.
Xiao-Qing HUANG ; Jin-Sen XU ; Xiao-Ran YE ; Xuan CHEN
Chinese journal of integrative medicine 2021;27(6):446-454
OBJECTIVE:
To evaluate the effect of the pulse width of electroacupuncture (EA) in the treatment of denervation-induced skeletal muscle atrophy in rats and examine the role of insulin-like growth factor 1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during EA.
METHODS:
Sciatic nerve functional index (SFI), muscle wet weight and the cross-sectional area (CSA) of the gastrocnemius muscle were analyzed after treatment in model rats with EA of various pulse widths (0.5, 50, 100 and 200 ms). The apoptosis index (AI) and paired box (PAX)3 and PAX7 protein expression were also determined. Further, the mRNA and protein expressions of components of IGF-1/PI3K/Akt pathway and their downstream targets were determined, along with the inhibiting effect of the pathway with a PI3-specific inhibitor.
RESULTS:
EA with a pulse width of 200 ms was found to have the best effect with regard to increasing SFI, CSA and muscle weight, decreasing AI, and increasing the expression of PAX3 and PAX7. The IGF-1/PI3K/Akt pathway was found to be activated by denervation, although the downstream forkhead box O (FoxO) pathway was not suppressed by its activation. The PI3K/Akt pathway and its downstream molecule mammalian target of rapamycin (mTOR) were up-regulated further by EA to promote muscle protein synthesis. Meanwhile, the expressions of downstream FoxO and F-box protein 32 (ATROGIN-1) were down-regulated to reduce protein degradation.
CONCLUSIONS
EA with 200-ms pulse width was found to have a more significant effect than 0.5-ms EA. The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway.
6.Respiratory infectious diseases and tissue "damage-repair" balance:pathological characteristics, treatment, and characteristics of traditional Chinese medicine.
Man-Li YANG ; Xin-Ke DU ; Xiao-Xi KAN ; Teng-Teng HAO ; Qing-Sen RAN
China Journal of Chinese Materia Medica 2021;46(24):6366-6376
Respiratory infectious diseases are important diseases causing major public safety events, posing a great threat to life, health, and social development. Effective control and scientific treatment of the diseases is the key basis for ensuring the stability and long-term development of the community of a shared future for human health. Although the pathogens of respiratory viral infectious diseases are diverse and the process is complex, the common pathological basis of their pathogenesis is characterized by the "damage-repair" functional imbalance of the immune microenvironment of the lesions, which leads to the subsequent structural and functional destruction of important organs. Therefore, the treatment should focus on antivirus and immunological regulation, strengthen the protection against immune injury, and promote the functional repair of damaged tissues. The above conclusions are the scientific core of host-directed therapies(HDT), which coincides with "human-disease co-treatment and healthy qi and pathogen interaction" in traditional Chinese medicine(TCM) theories. Under the support of TCM and western medicine theories, the complete pathological chain "infection-immunity-injury" of respiratory viral infectious diseases is integrated with dynamic change in "healthy qi-pathogen" in TCM to transform the treatment focus from the diseases to the patients. It is possible to fundamentally correct the "damage-repair" imbalance in the disease state, change the environment for disease development, and bring benefits to patients by strengthening human intervention, maintaining immune homeostasis, enhancing the protection of tissues and organs, and promoting the repair and regeneration of damaged tissues. This study focused on the common and key pathological processes of respiratory infectious diseases, especially the immune damage caused by the viral infection, to seek effective prevention and treatment strategies, review relevant theoretical progress, summarize effective drug candidates, prospect future research and development, and highlight the therapeutic characteristics of TCM.
Drugs, Chinese Herbal/therapeutic use*
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Humans
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Medicine, Chinese Traditional
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Respiratory Tract Infections/therapy*
7.Protective effects of three phenylallyl compounds from Guizhi decoction ox-LDL-induced oxidative stress injury of human brain microvascular endothelial cells.
Xiao-Dong LI ; Li-Wei GU ; Qing-Sen RAN ; Pan ZHOU ; Xiao-Ling ZHAN ; Cang-Hai LI ; Ting-Liang JIANG
China Journal of Chinese Materia Medica 2016;41(12):2315-2320
The main objective of this research is to observe protective effects of three phenylallyl compounds(cinnamyl alcohol,cinnamaldehyde and cinnamic acid)from Guizhi decoction against ox-LDL-induced oxidative stress injury on human brain microvascular endothelial cells(HBMEC).In this study,the toxicity and optimal protective concentration of three phenylallyl compounds from Guizhi decoction were determined by MTT assay.The HBMEC were divided into control group(DMSO),model group(ox-LDL),tert-butylhydroquinone (t-BHQ) group,cinnamyl alcohol group, cinnamaldehyde group and cinnamic acid group.The model group were treated with ox-LDL (50 mg•L⁻¹)for 24 h,other groups were separately treated with t-BHQ, cinnamyl alcohol, cinnamaldehyde and cinnamic acid of 20 μmol•L⁻¹, and exposed to ox-LDL (50 mg•L⁻¹) for 24 h at the same time.The survival rate of HBMEC was detected by MTT assay,reactive oxygen species(ROS) production of injured cells were detected using laser scanning confocal microscope (LSCM),the content of SOD, MDA, eNOS and NO in HBMEC was determined by ELISA, and the expressions of Nrf2 mRNA were detected by quantitative Real-time PCR(qRT-PCR).The results shows that oxidative stress injury of HBMEC could be induced by ox-LDL, the three phenylallyl compounds from Guizhi decoction did not affect morphology and viability of normal HBMEC.Compared with model group, the three phenylallyl compounds from Guizhi decoction could improve the above oxidative stress status and up-regulate Nrf2 mRNA expressions in injured HBMEC(P<0.05, P<0.01) .These findings suggested that the three phenylallyl compounds from Guizhi decoction have certain protective effects against ox-LDL-induced oxidative stress injury on HBMEC(cinnamaldehyde> t-BHQ> cinnamic acid>cinnamyl alcohol),the protective mechanism maybe related to regulation of antioxidant enzymes gene expression in HBMEC by Nrf2.
8.Relationship Between Immune Checkpoint and Autoimmune Disease
Qing-sen RAN ; Qi LI ; Li LIU ; Li-dong SUN ; Qing YANG ; Yu-jie LI ; Ying CHEN ; Ya-jie WANG ; Xiao-gang WENG ; Wei-yan CAI ; Xiao-xin ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(18):188-195
The normal immune system has the ability to distinguish between "self" and "non-self". Because of its dynamic balance of "immune activity-immune tolerance", it will produce immune response to the non-self antigen, but with no response or weak response to the self-antigen. However, if the balance was broken, T cell in the abnormal immune activation state will respond continually to the self-antigen, with an abnormal immune response, which caused autoimmune disease. Pathologically, "invalid" immune recognition and immune response become the main causes for autoimmune diseases. Co-stimulatory molecule is an important link between Attach antigen presenting cells(APC) and immune cells (T cell and B cell). Studies have proved that excessive co-stimulation and/or insufficient co-inhibition could cause detect of self-tolerance and induce autoimmunity. Although co-stimulatory and co-inhibitory pathways have a significant impact on all ADS, this paper focuses on their effect on two systemic autoimmune diseases [systemic lupus erythematosus (SLE) and rheumatoid arthritis(RA)] and two organ-specific autoimmune diseases [multiple sclerosis (MS) and type 1 diabetes (T1DM)], in order to discuss the pathogenesis and relationship between co-stimulatory molecules and autoimmune diseases.
9.Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling.
Li-Na YANG ; Xin-Ke DU ; Li LIU ; Man-Jing LI ; Qing-Sen RAN ; Qing YANG ; Li-Dong SUN ; Yu-Jie LI ; Ying CHEN ; Xiao-Xin ZHU ; Qi LI
China Journal of Chinese Materia Medica 2023;48(1):5-12
Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.
Humans
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Multiple Sclerosis/pathology*
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Remyelination/physiology*
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Myelin Sheath/pathology*
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Inflammation/drug therapy*
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Homeostasis
10.Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model.
Qi LI ; Jie YIN ; Qing-Sen RAN ; Qing YANG ; Li LIU ; Zheng ZHAO ; Yu-Jie LI ; Ying CHEN ; Li-Dong SUN ; Ya-Jie WANG ; Xiao-Gang WENG ; Wei-Yan CAI ; Xiao-Xin ZHU
China Journal of Chinese Materia Medica 2019;44(11):2317-2323
This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.
Acute Lung Injury
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microbiology
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Animals
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Bacterial Infections
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drug therapy
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Bronchoalveolar Lavage Fluid
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Capsules
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Chemokine CCL2
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metabolism
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Chemotaxis
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Drugs, Chinese Herbal
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pharmacology
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Humans
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Lipopolysaccharides
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Lung
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Macrophages
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drug effects
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Mice
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RAW 264.7 Cells
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Random Allocation
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THP-1 Cells
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Tumor Necrosis Factor-alpha
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metabolism