Jun Zhang

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons (DNs). Currently, there is no treatment that can cure PD. Deep brain stimulation has been used to treat PD due to its good effectiveness, but there are safety issues. Therefore, noninvasive electrical stimulation (NES) may be an effective and safe strategy for the treatment of PD. Here, we performed NES treatment and NES combined with human adipose‐derived stem cells‐induced DN transplantation (NES‐DN) on the PD monkey model to explore the therapeutic effect of NES on PD. The results show that NES or NES‐DN can increase dopamine levels, improve mitochondrial dysfunction, reduce neuroinflammation, enhance synaptic function, and protect TH neurons, thereby improving the movement disorders of PD. Moreover, NES/NES‐DN may exert immunomodulatory effects by regulating serpin family A member 3 in PD monkeys. Our results support the scientific basis and preclinical evidence for NES in the treatment of PD. Not only does NES alone improve PD, but NES combined with stem cell therapy can greatly enhance the therapeutic effect of PD.

Background: Ginsenoside Rc has been known for its promising protective effects against myocardial injury, including inflammation, apoptosis, oxidative stress, and related pathways. However, the underlying molecular mechanisms behind these effects still need to be explored. The purpose of this study was to explore the therapeutic effect of Ginsenoside Rc on acute myocardial infarction (MI) and the molecular mechanism behind it. Methods: MI mouse model and oxygen-glucose deprivation (OGD) cardiomyocyte injury model were established and Ginsenoside Rc was treated. Troponin I3 (TNNI3)/C-reactive protein (CRP) expression was altered by plasmid transfection or lentiviral vector injection. Myocardial histopathological changes were evaluated by hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining. The changes in inflammatory cytokines in cells and tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). Commercial kits were used for the assessment of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH). Western blot was used to analyze cleaved caspase-3 protein expression in cells and tissues. The apoptosis rate of cardiomyocytes was measured by flow cytometry. The interaction between TNNI3 and CRP was detected by co-immunoprecipitation (CO-IP) assay. Results: TNNI3/CRP expression was abnormally high in MI, and Ginsenoside Rc decreased their relative expression (p < 0.05). Ginsenoside Rc administration reduced inflammation and apoptosis in MI mice and OGD-injured cardiomyocytes (p < 0.05). Ginsenoside Rc administration or TNNI3 knockdown improved the myocardial tissue injury in MI mice (p < 0.05). The therapeutic effect of Ginsenoside Rc on myocardial injury in MI mice was weakened by overexpressing TNNI3 (p < 0.05). Similarly, its therapeutic effect on OGD cardiomyocyte injury was also weakened by enhancing TNNI3 and CRP (p < 0.05). TNNI3 and CRP also interacted in cardiomyocytes. Conclusions: Ginsenoside Rc improves MI-induced cardiomyocyte apoptosis and inflammation by inhibiting the TNNI3/CRP axis. The study shows that Ginsenoside Rc can serve as a potential drug for the future treatment of MI.

The main pathophysiological abnormalities in type 2 diabetes (T2D) include pancreatic β-cell dysfunction and insulin resistance. Due to hyperglycemia, patients receive long-term treatment. However, side effects and drug tolerance usually lead to treatment failure. GuaLouQuMaiWan (GLQMW), a common traditional Chinese medicine (TCM) prescription, has positive effects on controlling blood sugar and improving quality of life, but the mechanism is still unclear. To decipher their molecular mechanisms, we used a novel computational systems pharmacology-based approach consisting of bioinformatics analysis, network pharmacology, and drug similarity comparison. We divided the participants into nondisease (ND), impaired glucose tolerance (IGT), and type 2 diabetes groups according to the WHO’s recommendations for diabetes. By analyzing the gene expression profile of the ND-IGT-T2D (ND to IGT to T2D) process, we found that the function of downregulated genes in the whole process was mainly related to insulin secretion, while the upregulated genes were related to inflammation. Furthermore, other genes in the ND-IGT (ND to IGT) process are mainly related to inflammation and lipid metabolic disorders. We speculate that 17 genes with a consistent trend may play a key role in the process of ND-IGT-T2D. We further performed target prediction for 50 compounds in GLQMW that met the screening criteria and intersected the differentially expressed genes of the T2D process with the compounds of GLQMW; a total of 18 proteins proved potential targets for GLQMW. Among these, RBP4 is considerably related to insulin resistance. GO/KEGG enrichment analyses of the target genes of GLQMW showed enrichment in inflammation- and T2D therapy-related pathways. Based on the RDKit tool and the DrugBank database, we speculate that (-)-taxifolin, dialoside A_qt, spinasterol, isofucosterol, and 11,14-eicosadienoic acid can be used as potential drugs for T2D via molecular docking and drug similarity comparison.

Background. Hyperplasia of mammary glands (HMG) is the breast disease with the highest clinical incidence. Many traditional Chinese medicine (TCM) doctors suggest that the treatment of HMG should be based on the left and right breast pain difference. However, these views are based on case reports, and an objective basis has not been established for treatment according to left-side and right-side differences. Methods. We enrolled 150 patients who met the clinical diagnostic criteria of HMG. The incidence bias was determined according to the score difference between bilateral breast pain and mass in patients with HMG. A left group, right group, and bilateral group were included, and TCM constitution was investigated in each group. Blood biochemical indicators were measured for 120 fasting patients. We conducted a network pharmacology study of the key herb qingpi and chenpi, which are used by TCM doctors to treat different lateral HMG. Results. In patients with biased onset of HMG, the results showed that the frequency and constitution score of stagnant blood in the L group were higher than those of the R group, and the frequency and constitution score of phlegm-dampness in the R group were higher than those of the L group. Both the L and R groups had high proportion of stagnant Qi. The results indicated that the concentration of coagulation factor VIII (FVIII) was higher in the L group than that in the R group, and the concentration of lipoprotein a (Lp-α) was higher in the R group than that in the L group. The results showed that sinensetin and neohesperidin contained in qingpi might interfere with platelet activation, thrombogenesis, prolactin signaling pathway, and atherosclerosis process, in removing blood stasis and eventually treating the left-leaning group of HMG patients. Sitosterol and citromitin contained in chenpi could regulate lipid metabolism by interfering with regulation of lipolysis in adipocytes, salivary secretion, estrogen signaling pathway, and thyroid hormone signaling pathway. Chenpi could eliminate phlegm turbidity and treat HMG patients in the right-leaning group. Conclusions. We preliminarily confirmed that the clinical pathogenesis of HMG is not a left-right equilibrium and TCM constitution, coagulation function, and lipid metabolism may be used as the objective basis for the difference between the left and right in HMG pathogenesis. For left-sided HMG patients, the doctor can consider qingpi, herb of activating blood and removing stasis, to treat HMG. However, for right-sided HMG, we think doctors should apply herb of activating Qi and eliminating phlegm, such as chenpi.

Depression is a common secondary symptom in neurodegenerative diseases (NDs) caused by the loss of neurons and glial cells. Recent research focuses on stem cell therapy to replace dead nerve cells, but the low efficiency of stem cell differentiation and short survival time are obstacles limiting the therapy’s effectiveness. Clinically, patients with different diseases cannot obtain the same effect by using the same cell therapy. However, traditional Chinese medicine (TCM) often uses syndrome differentiation to determine the treatment plan for NDs. Based on TCM syndrome differentiation and treatment, this article summarizes the advantages of Chinese herbal medicine combined with stem cell therapy, mainly for the effects of various herbs on diseases and stem cells, including prolonging the survival time of stem cells, resisting inflammation, and antidepressant-like effects. In particular, it analyzes the unique pathways of the influence of drugs and acupuncture on different therapies, seeking to clarify the scientific TCM system. This review mainly elaborates on the treatment of secondary depression in TCM and the advantages of a herbal combined stem cell therapy in various methods. We believe it can provide a new clinical concept for secondary depression to obtain good clinical effects and reduce the risks borne by patients.