1.Early recumbent treadmill training can promote the recovery of balance and functional independence of children after stem cell transplantation
Huanlan XU ; Guangjun LIANG ; Hewei ZHANG ; Hongliang HUO ; Fan WEN ; Qin GU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(3):232-236
Objective:To observe any effect of early recumbent treadmill training on the balance and functional independence during hospitalization of children who have received hematopoietic stem cell transplantation (HSCT).Methods:This was a retrospective analysis of 106 children who had received HSCT. Sixty-nine of them were qualified for study. Of those, 32 had performed recumbent treadmill training and the other 37 had not. The children in both groups received routine clinical treatment and nursing care, and also health education advocating exercise and giving exercise programs before and after the transplantation. The daily exercise was conducted with the help of parents. It lasted 20 to 30 minutes each time, 4 or 5 times a week. The treadmill group additionally spent 30 minutes training on a recumbent treadmill 5 times a week for 6 weeks. Balance, functional independence and fatigue levels were quantified before and after the treatment using the Berg Balance Scale (BBS), the Functional Independence Measure for Children (WeeFIM) and the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale.Results:After the 6 weeks, significant improvement was observed in the experimental group′s average BBS score, motor function domain score, total WeeFIM score, general fatigue, and sleep/rest fatigue. All were then significantly better than the non-treadmill group′s results.Conclusion:Early recumbent treadmill training can promote the recovery of balance and functional independence of children after HSCT.
2.Advances in the mechanism-of-action of circRNA in Parkinson's disease
Juan LIU ; Yanjie LI ; Hewei QIN ; Luyao MA ; Nannan ZHAO ; Zhenhua XU
Chinese Journal of Comparative Medicine 2024;34(2):161-166
PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.
3.Effects of Lipopharyngeal Qibi Formula on swallowing function and apoptosis in central cortical swallowing neurons in rats after stroke
Yanjie LI ; Sijin LI ; Xiaoqiong HUA ; Hewei QIN ; Xiaoqin JIN ; Zhixin ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(16):2527-2533
BACKGROUND:The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy,and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing.Therefore,this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology,thereby developing new ideas for the exploration of their mechanisms. OBJECTIVE:To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action. METHODS:Thirty-eight Sprague-Dawley rats were randomly divided into model group(n=14),treatment group(n=14)and sham-operated group(n=10).Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method.At 6 hours after modeling,neurological function was scored,and rats with a score of 2 were selected for subsequent experiments.The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage.Changes in body mass,24-hour food and water intake were recorded on days 2,7,14 and 30.The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30.After the swallowing test,the ischemic area of the brain in each group was measured by TTC staining.The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry.The mRNA and protein expression levels of BCL-2 and BAX in the insula,premotor cortex,cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham-operated group,the body mass,24-hour food intake and water intake were reduced,the swallow initiation response time was prolonged,and the number of swallows was reduced in the treatment and model groups at day 14 of gavage(P<0.05).Compared with the model group,the body mass,24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage(P<0.05),but were still lower than those in the sham-operated group.Compared with the model group,the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group,but the number of swallows was still significantly lower than that in the sham-operated group(P<0.05).Cerebral ischemia area was reduced in the treatment group compared with the model group,and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group,but it was still significantly lower than that in the sham-operated group(P<0.05).Compared with the model group,the expression of BCL-2 mRNA and protein in the insula,cingulate cortex and thalamus of rats in the treatment group were significantly increased,the expression of BAX mRNA and protein were significantly decreased,and the BCL-2/BAX ratio was significantly increased(P<0.05).To conclude,the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time,as well as 24-hour food intake,body mass and other swallowing-related indexes in rats with post-stroke dysphagia.The mechanism of action may be achieved by improving the area of cerebral ischemia,inhibiting the apoptosis of neuronal cells in the insula,cingulate cortex and thalamus of rats,thus improving the regulation of the higher centers on the medulla oblongata swallowing center,and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius.
4.Mechanistic of Modified Chunzetang in Treating Spinal Cord Injury-induced Urinary Retention in Rats Based on JNK/p38 MAPK Signaling Pathway
Yupu WANG ; Yanjie LI ; Hewei QIN ; Haoyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):30-38
ObjectiveTo investigate the effects of modified Chunzetang on urinary retention in rats with spinal cord injury (SCI) and the c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway. MethodBefore modeling, 10 of the 70 female SD rats were randomly selected to assign to the blank group, and 10 to the sham group. The remaining 50 rats were used to prepare a SCI-induced urinary retention model using the spinal cord transection method. The model rats were randomly divided into model group, low-dose modified Chunzetang group, high-dose modified Chunzetang group, and inhibitor group. After modeling, the blank group, sham group, and inhibitor group were given 2 mL of saline by gavage. The high-dose and low-dose groups of modified Chunzetang were given modified Chunzetang at 28.8 g·kg-1 and 14.4 g·kg-1 by gavage, respectively. The inhibitor group was injected intraperitoneally with the JNK inhibitor SP600125 twice a week at a dose of 15 mg·kg-1. All rats were gavaged for a total of 28 days. Urodynamic and bladder muscle tension tests were conducted to evaluate bladder function. Hematoxylin-eosin (HE) staining was performed to observe the morphology of bladder smooth muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of JNK, phosphorylated (p)-p38 MAPK, B cell lymphoma-2 (Bcl-2), and cysteinyl aspartate-specific proteinase-3 (Caspase-3). Western blot was used to detect the expression levels of p-JNK, p-p38 MAPK, ETS-like protein-1 (ELK-1), and activator protein-1 (AP1) in the detrusor muscle. Immunofluorescence was used to detect the expression levels of p-JNK, p-p38 MAPK, and AP1. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was conducted to measure cell apoptosis. ResultCompared with blank group and sham group, the model group showed a significant increase in maximum bladder capacity and bladder compliance, and a significant decrease in leak point pressure. The minimum contraction force was increased, and the contraction frequency was significantly decreased (P<0.01). The structure of bladder smooth muscle was disordered, with a large number of vacuolar cells, tissue edema, mononuclear cell infiltration, obvious hemorrhage, and a trend towards fibrosis in connective tissue. TUNEL positive cells increased significantly. The protein expression levels of p-JNK, p-p38 MAPK, AP1, and ELK-1 were significantly increased (P<0.01). Compared with model group, all intervention groups showed significant improvement in urodynamic and bladder muscle contraction tests. In the low-dose modified Chunzetang group, the levels of p-p38 MAPK and Caspase-3 was decreased (P<0.05,P<0.01). The levels of JNK, p-p38 MAPK and Caspase-3 in the high-dose group were significantly decreased (P<0.01), and the level of Bcl-2 was significantly increased (P<0.01). The expression levels of p-JNK, p-p38 MAPK, and AP1 proteins were significantly reduced (P<0.01), and ELK-1 protein expression was decreased (P<0.05). The positive rate of p-JNK and AP1 receptors was significantly decreased (P<0.01). The positive cell rate was significantly decreased (P<0.01). The high-dose modified Chunzetang group was positioned between the low-dose group and the inhibitor group, with no significant difference compared to the inhibitor group. ConclusionModified Chunzetang can improve urinary retention in SCI and enhance the contraction force of bladder smooth muscle. This effect is related to the inhibition of the JNK/p38 MAPK signaling pathway activation, thereby reducing apoptosis of bladder smooth muscle cells.
5.Tongmai Kaiqiao Pills Treat Vascular Dementia in Rats by Regulating Mitochondrial Autophagy via HIF-1α/BNIP3 Signaling Pathway
Huimin DING ; Yanjie LI ; Hewei QIN ; Chenyuan HAO ; Nannan ZHAO ; Zhenhua XU ; Mengyan SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):52-60
ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α (HIF-1α)/adenovirus E1B 19 kD-interacting protein 3 (BNIP3) signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia (VD). MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group, where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups: model, high-, medium-, and low-dose (27.6, 13.8, 6.9 g·kg-1, respectively) Tongmai Kaiqiao pills, donepezil hydrochloride (0.45 mg·kg-1), and combination (27.6 g·kg-1 Tongmai Kaiqiao pills + 2.5 mg·kg-1 HIF-1α inhibitor YC-1) groups. After 4 weeks of treatment, samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes, respectively, in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α, BNIP3, Beclin-1, and microtubule-associated protein 1 light chain 3B (LC3B) in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α, BNIP3, and LC3B in the hippocampal tissue. ResultCompared with the sham group, the model group showed prolonged escape latency (P<0.01), decreased number of platform crossings (P<0.01), reduced and disarranged neuronal layers in the hippocampal region, decreased number of Nissl bodies, disrupted mitochondrial cristae, damaged mitochondrial double-membrane structures, increased number of autophagosomes, upregulated expression of HIF-1α, BNIP3, beclin1, and LC3B (P<0.05, P<0.01), and enhanced fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.05, P<0.01). Compared with the model group, Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform (P<0.01) and increased the number of platform crossings (P<0.01). Moreover, the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies, alleviated the damage, increased the number of autophagosomes, upregulated the expression of HIF-1α, BNIP3, Beclin1, and LC3B (P<0.05, P<0.01), and enhanced the fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.05, P<0.01). Compared with high-dose Tongmai Kaiqiao pills, the combination group prolonged the escape latency (P<0.01), reduced the number of crossing platforms (P<0.01), decreased the number of hippocampal neurons, aggravated the damage, decreased the number of Nissl bodies and autophagosomes, downregulated the expression of HIF-1α, BNIP3, beclin1, and LC3B (P<0.01), and decreased the fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.01). ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy, clear damaged mitochondria, provide energy for healthy cells, reduce neuronal cell death, and restore the brain function, thereby reducing ischemic damage to the hippocampal tissue, improving learning and memory abilities, and exerting therapeutic effects on VD in rats.
6.Research progress of the mechanism of traditional Chinese medicine in the prevention and treatment of athero-sclerosis based on miRNA regulation of vascular endothelial cell injury
Dandan LIU ; Hewei QIN ; Yang GAO ; Mengyan SUN ; Mengnan WANG ; Yuqing NIU ; Xuemei SONG
China Pharmacy 2023;34(12):1524-1528
The injury of vascular endothelial cells is not only the initial condition to promote the occurrence of early atherosclerosis (AS) plaques, but also an important link in the pathogenesis of AS. The microRNA (miRNA), as an important medium of intercellular communication and gene regulatory factor, can affect vascular endothelial function and participate in the development of AS. The molecular mechanism of miRNA’s multi-target intervention in vascular endothelial cell injury has become a hot topic in the research of cardiovascular diseases. Monomers of traditional Chinese medicines such as ginsenoside Rb2 and paeonol, as well as traditional Chinese medicine for resolving phlegm and removing blood stasis could regulate miRNA to improve endothelial cell inflammation; astragaloside Ⅳ, dihydromyricetin and notoginsenoside could target miRNA and inhibit vascular endothelial oxidative stress; Danhong injection, Jianpi qutan and huayu prescription and paeonol could affect endothelial autophagy through miRNA; resveratrol, Bushen huoxue formula and Bushen tongmai formula could inhibit vascular endothelial aging by miRNA; dendrobine played an active role in regulating miRNA and improving endoplasmic reticulum stress. In the future, more in- depth research is needed on the effectiveness, mechanism of action, diagnosis and treatment plans, and safety of targeted regulation of miRNA for AS therapy by traditional Chinese medicine.