Treatment of Depression with Acupuncture Based on Pathophysiological Mechanism.

Depression is a prevalent mental disorder and has a profound impact on an individual's psychological and physical well-being. It is characterized by a persistently depressed mood, loss of interest, energy loss, and cognitive dysfunction. In recent years, more and more people have changed to mental diseases, such as depression, anxiety, mania and so on. In the incidence of depression, covering all ages, but still mainly young and middle-aged women. Traditional treatments for depression mainly rely on medication and psychotherapy, but these methods are not effective for all patients and are often accompanied by certain side effects. Therefore, finding safe and effective alternative or adjuvant treatments has become a priority. Here we highlight the research progress of acupuncture in the treatment of depression and to explore the mechanism of acupuncture in the treatment of depression. Acupuncture treatment of depression is an ancient and effective method, the mechanism involves multiple biological pathways, for example, by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammatory and other effects, improving emotional state and play an antidepressant role. To provide evidence to support the widespread use of acupuncture in clinical practice. We hope to provide new treatment ideas and methods for patients with depression, and even reduce the incidence of depression.

Wrist-ankle acupuncture for the treatment of acute orthopedic pain after surgery: a meta-analysis.

BACKGROUND: Wrist-ankle acupuncture (WAA) has been reported in the treatment of acute pain in orthopedic surgery. However, the effects of WAA on acute pain were controversial in the current studies. Therefore, the purpose of this meta-analysis was to critically evaluate the effects of WAA on acute pain in orthopedic surgery. METHODS: Several digital databases were searched from the inception of databases to July 2021, including CNKI, VIP, Wanfang, CBM, Pubmed, Cochrane Central Register of Controlled Trials, Embase, Medline, and Web of Science Core Collection. The risk of bias was evaluated using the Cochrane collaboration criteria. The primary outcome indicators included pain score, pain killer dosage, analgesia satisfaction, and adverse reaction incidence. All analyses were performed with Review Manager 5.4.1. RESULT: A total of 10 studies with 725 patients with orthopedic surgery (intervention group: 361, control group: 364) were included in this meta-analysis. The results demonstrated that the pain score of the intervention group was lower than the control group, and the difference was statistically significant [MD = - 0.29, 95%CI (- 0.37, - 0.21), P < 0.0001]. Compared with the control group, the patient in the intervention group used smaller amounts of pain killer [MD = - 0.16, 95%CI (- 0.30, - 0.02), P = 0.02]. The satisfaction of patients on pain relief was also higher in the intervention group, and the difference was statistically [OR = 0.25, 95%CI (0.15,0.41), P < 0.0001]. CONCLUSION: WAA has a certain effect on acute pain in orthopedic surgery, and the effect of WAA combined with other therapies is better than that of not using WAA therapy.

Analysis of Triterpenoid Saponins Reveals Insights into Structural Features Associated with Potent Protein Drug Enhancement Effects.

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents was assessed on the basis of cytotoxicity, endosomal escape promotion, and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 106 to 109 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP-treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

Screening and characterization of a novel high-efficiency tumor-homing cell-penetrating peptide from the buffalo cathelicidin family.

Targeted delivery of antitumor drugs is especially important for tumor therapy. Cell-penetrating peptides (CPPs) have been shown to be very effective drug carriers for tumor therapy. However, most CPPs lack tumor cell specificity. Here, we identified a highly efficient CPP, CAT, from the newly identified buffalo-derived cathelicidin family, which exhibits a preferential binding capacity for multiple tumor cell lines and delivers carried drug molecules into cells. CAT showed an approximately threefold to sixfold higher translocation efficiency than some reported cell-penetrating antimicrobial peptides, including the well-known classical CPP TAT. Moreover, the delivery efficiency of CAT was greater in a variety of tested tumor cells than in normal cells, especially for the human hepatoma cell line SMMC-7721, for which delivery was 7 times more efficient than the normal human embryonic lung cell line MRC-5, according to fluorescent labeling experiment results. CAT was conjugated to the Momordica charantia-derived type-I ribosome-inactivating protein MAP 30, and the cytotoxicity of the MAP 30-CAT fusion protein in the tumor cell line SMMC-7721 was significantly enhanced compared with that of the unconjugated MAP 30. The IC50 value of MAP 30-CAT was approximately 83 times lower than the IC50 value of the original MAP 30. Interestingly, the IC50 value of MAP 30 alone for MRC-5 was approximately twofold higher than the value for SMMC-7721, showing a small difference. However, when MAP 30 was conjugated to CAT, the difference in IC50 values between the two cell lines was significantly increased by 38-fold. The results of the flow cytometric detection of apoptosis revealed that the increase in cytotoxicity after CAT conjugation was mainly caused by the increased induction of apoptosis by the fusion protein. These results suggest that CAT, as a novel tumor-homing CPP, has great potential in drug delivery applications in vivo and will be beneficial to the development of tumor therapeutics.

Enhanced anti-tumor activity of trichosanthin after combination with a human-derived cell-penetrating peptide, and a possible mechanism of activity.

Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP-I) and renowned Chinese traditional medicine, displays a broad spectrum of biological and pharmacological properties. Particularly, its anti-tumor activity has received a great deal of attention. However, the cellular mechanism for TCS uptake varies with different tumor cell lines, leading to discrepancies in its reported ability to penetrate cells. In this study, HBD, a human derived cell-penetrating peptide (CPP), was used to improve the delivery of TCS into several types of tumor cells, including HeLa cells. Recombinant TCS (rTCS) with or without the fused HBD peptide was expressed in Escherichia coli cells and successfully purified by Ni-NTA affinity chromatography. The cellular uptake efficiency of FITC-labelled-rTCS-HBD was observed in HeLa cells and compared with the uptake efficiency of non-HBD conjugated rTCS under the same conditions using laser confocal microscopy. Moreover, the IC50 value of rTCS-HBD in the tested tumor cells was much lower than that of rTCS, indicating that HBD could efficiently deliver the rTCS into tumor cells. When compared with rTCS, rTCS-HBD induced higher rates of apoptosis in HeLa cells as analyzed by flow cytometry. Furthermore, the apoptotic events observed in HeLa cells incubated with HBD-fused rTCS included activation of Caspase-9, decrease in the Bcl-2/Bax ratio, and cleavage of PARP. These results strongly suggest the participation of mitochondria in apoptosis. This report illustrates one possible method for achieving the efficient transport of TCS into cells using a CPP as a vector, and increases the likelihood that TCS can be used in the clinic.

The efficacy and safety of the Shaoyao Shujin tablet for knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is a major public health issue causing chronic disability as well as a burden on healthcare resources. In China, a herbal drug tablet has been used as an effective and conventional therapy to alleviate clinical symptoms caused by KOA. However, evidence gathered from systematic reviews or randomized controlled trials that validated herbal drugs for the management of osteoarthritic pain is weak. The purpose of this study is to explore the efficacy and safety of the Shaoyao Shujin tablet for the management of KOA in a short-term study. METHODS/DESIGN: This trial is a multicenter randomized, double-blind, placebo-controlled study. A total of 276 patients will be randomized into 3 groups: (1) the high-dose Shaoyao Shujin tablet group (HD group), (2) the low-dose Shaoyao Shujin tablet group (LD group), and (3) the placebo tablet group (control group). In the three groups, four tablets will be administered three times per day for 6 weeks. Follow-up will be at regular intervals during a 10-week period with the Western Ontario and McMaster Universities Index (WOMAC) score, visual analog scale (VAS) score, and rescue medication use assessed as outcome measures. DISCUSSION: This study will provide clinical evidence on the efficacy and safety of the Shaoyao Shujin tablet in treating KOA. TRIAL REGISTRATION: Chinese Cochrane Center ChiCTR-IPR- 15006194 , registered 4 April 2015.

Clinical effectiveness and micro-perfusion alteration of Jingui external lotion in patients with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis is a major cause of disability in the aging population. Based on pathological, magnetic resonance imaging (MRI) and arthroscopy studies, progressive osteoarthritis involves all tissues of the joint and includes bone marrow lesions, synovial proliferation, fat pad inflammation, and high subchondral bone turnover. Recent research suggests that abnormal perfusion in bone marrow lesions, fat pads, and subchondral bone is associated with pain in knee osteoarthritis, and that dynamic contrast-enhanced MRI is a promising method for studying micro-perfusion alteration in knee osteoarthritis. Traditional Chinese Medicine approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the Jingui external lotion is the preferred and most commonly used method in China to reduce pain in patients with knee osteoarthritis; however, there is a lack of validated evidence for its effectiveness. The purpose of this study is to explore the effectiveness of Jingui external lotion for the management of painful knee osteoarthritis in a short-term study. In addition, we will assess micro-perfusion alteration in the patellar fat pad as well as the femur and tibia subchondral bone via dynamic contrast-enhanced MRI. METHODS/DESIGN: This trial is a randomized, controlled study. A total of 168 patients will be randomized into the following two groups: 1) the Jingui external lotion group (treatment group); and 2) the placebo lotion group (control group). In both groups, lotion fumigation and external washing of the patients' knees will be administered twice a day for 14 consecutive days. Follow-up will be at regular intervals during a 4-week period with a visual analog scale to assess pain, and additional characterization with the Western Ontario and McMaster Universities Index score; rescue medication will be recorded as the extent and time pattern. In addition, micro-perfusion alteration in the patellar fat pad, femur and tibia subchondral bone will be assessed via dynamic contrast-enhanced MRI. DISCUSSION: This study will provide clinical evidence of the efficacy of Jingui external lotion in treating knee osteoarthritis, and it will be the first randomized controlled trial to investigate micro-perfusion alteration of knee osteoarthritis with Traditional Chinese Medicine external lotion via dynamic contrast-enhanced MRI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-14004727 ; 31 May 2014.

[Regulation of single herb pilose antler on the expression of Smad2 and Smad3 in the cartilage of OA rats: an experimental research].

OBJECTIVE: To observe the effect of single herb pilose antler (PA) on the expression of Smad2 and Smad3 in the cartilage of osteoarthritis (OA) rats. METHODS: One hundred 3-month old female healthy SD rats, (200 +/- 20) g, were recruited and routinely fed for 1 week. They were randomly divided into 5 groups, i.e., the low dose PA group, the high dose PA group, the normal saline control group, the model group, and the normal control group, 20 in each group. The model was prepared using classic Hulth method except the normal control group. After 6-week modeling, the model was confirmed successful by pathologic observation. PA at 0.021 g/100 g and 0.084 g/1 00 g was given by gastrogavage to rats in the low dose PA group and the high dose PA group respectively. Normal saline was administered to those in the normal saline control group. No treatment was given to rats in the normal control group and the model group. Bilateral knee cartilages were harvested at week 2,4, and 6. mRNA and protein expressions of Smad2 and Smad3 were detected by immunohistochemical assay, fluorescent quantitative PCR, and Western blot. RESULTS: OA model was successfully prepared by pathological observation. Results of immunohistochemical assay showed that Smad2 and Smad3 expressed extensively in the cartilage, and located inside the chondrocyte membrane. Compared with the model group, mRNA expression of Smad2 and Smad3 obviously increased in the low dose PA group and the high dose PA group at week 2, 4, and 6, showing statistical difference (P < 0.05). Compared with the same group at week 4 after gastrogavage, mRNA expression of Smad2 and Smad3 obviously decreased in the low dose PA group and the high dose PA group at week 6, showing statistical difference (P < 0.05). Compared with the model group, protein expression of Smad2 and Smad3 obviously increased in the chondrocytes of the low dose PA group and the high dose PA group at week 2 and 4, showing statistical difference (P < 0.01). Compared with the same group at week 2 after gastrogavage, protein expression of Smad2 and Smad3 obviously increased in the low dose PA group and the high dose PA group at week 4, showing statistical difference (P < 0.01). Compared with the same group at week 4 after gastrogavage, protein expression of Smad2 and Smad3 obviously decreased in the low dose PA group and the high dose PA group at week 6, showing statistical difference (P < 0.01). CONCLUSIONS: (1) The pilose antler could repair cartilages by regulating mRNA and protein expressions of Smad2 and Smad3. (2) Up-regulating mRNA and protein expressions of Smad2 and Smad3 might be one of important mechanisms for the pathogenesis of OA.

Component analysis of Chinese medicine and advances in fuming-washing therapy for knee osteoarthritis via unsupervised data mining methods.

OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis (KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods. METHODS: Chinese medicine recipes for fuming-washing therapy for KOA were collected and recorded in a database. The correlation coefficient among herbs, core combinations of herbs, and new prescriptions were analyzed using modified mutual information, complex system entropy cluster, and unsupervised hierarchical clustering, respectively. RESULTS: Based on analysis of 345 Chinese medicine recipes for fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred frequently, and 12 core combinations were found. Five new fuming-washing recipes for KOA were developed. CONCLUSION: Chinese medicines for fuming-washing therapy of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs, blood-activating and stasis-resolving herbs, and wind-dampness-dispelling and heat-clearing herbs. The treatment of fuming-washing therapy for KOA also includes dispelling wind-dampness and dispersing cold, activating blood and resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao (Herba Speranskiae Tuberculatae), Honghua (Flos Carthami), Niuxi (Radix Achyranthis Bidentatae), Shenjincao (Herba Lycopodii Japonici), Weilingxian (Radix et Rhizoma Clematidis Chinensis), Chuanwu (Radix Aconiti), Haitongpi (Cortex Erythrinae Variegatae), Ruxiang (Olibanum), Danggui (Radix Angelicae Sinensis), Caowu (Radix Aconiti Kusnezoffii), Moyao (Myrrha), and Aiye (Folium Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for KOA.