Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach.

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.

GuiLu-ErXian Glue extract promotes mesenchymal stem cells (MSC)-Induced chondrogenesis via exosomes release and delays aging in the MSC senescence process.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. AIM OF THE STUDY: The aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. METHODS: Using human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-ß1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated ß-Galactosidase staining. RESULTS: The results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 µg/mL, 0.3 µg/mL in vitro. In vivo, GLEXG at the dose of 0.3 µg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. CONCLUSION: we conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 µg, i.a.) rescued cartilage defects in rat OA knee model.

Effect of Catgut Embedment in Du Meridian Acupoint on Mental and Psychological Conditions of Patients with Gastroesophageal Reflux Disease.

OBJECTIVE: To observe the influence of the catgut-embedding method in Du Meridian acupoint on the mental and psychological state of patients with gastroesophageal reflux disease (GERD) and analyze its possible mechanism. METHODS: According to the random number table, 60 patients with GERD were randomly divided into groups of acupoint catgut embedding and Western medicine, 30 cases in each group. The acupoint group was given catgut embedment in the positive reaction points along the Du Meridian, while the Western medicine group received lansoprazole tablet. They were both treated for six weeks. Scores of Gastroesophageal Reflux Disease Questionnaire (GerdQ), Zung's Self-Rating Anxiety Scale (SAS), Zung's Self-Rating Depression Scale (SDS), and Health-Related Quality of Life Scale for GERD (GERD-HRQL) were measured before and after treatment to analyze and evaluate the differences of symptom scores and mental and psychological conditions between the two groups. RESULTS: (1) The scores of GerdQ, GERD-HRQL, SAS, and SDS in the two groups both significantly decreased after treatment (P < 0.05), and those of the acupoint group were much lower than the Western medicine group (P < 0.05). (2) The total effective rate was 90.00% in the acupoint group and 53.33% in the Western medicine group, with a statistically significant difference (P < 0.05). (3) The correlation coefficients r between the GerdQ score and scores of SAS and SDS were 0.563 and 0.322, respectively, and those between the GERD-HRQL score and scores of SAS and SDS were, respectively, 0.506 and 0.435. CONCLUSION: (1) The main symptoms of GERD patients, such as acid reflux and heartburn, mental and psychological condition, and quality of life, were all improved in the two groups, but the efficacy in the acupoint group is superior to that of the Western medicine group. (2) The clinical symptoms and scores of patients' quality of life are positively correlated with the degree of their anxiety and depression. (3) The acupoint catgut-embedding method can effectively regulate the anxiety and depressive symptoms of patients, which complements the efficacy of proton-pump inhibitors and benefits a wider range of population.

The Effectiveness of Electroacupuncture for Functional Constipation: A Randomized, Controlled, Clinical Trial.

Background. Electroacupuncture (EA) has been reported to treat functional constipation (FC). The aim of this study was to investigate the efficacy and safety of EA with different needle insertion method for FC. Methods. Sixty-seven participants were randomly assigned to control (EA with shallow puncture) and EA (with deep puncture) groups. Every patient received 5 treatments per week in the first two weeks, then 3 treatments per week during the following six weeks. Complete spontaneous bowel movements (CSBM), spontaneous bowel movements (SBM), Bristol stool scores (BSS), and Patient Assessment of Constipation Quality of Life (PAC-QOL) were assessed. Results. Both shallow and deep EA significantly increased CSBM frequency compared to the baseline. CSBM was increased from 0.50 ± 0.59/wk to 2.00 ± 1.67/wk with deep EA and from 0.48 ± 0.59/wk to 1.33 ± 1.09/wk with shallow EA (P < 0.05, resp.). Similar finding was noted in SBM. Deep EA was more potent than shallow EA (P < 0.05) during the treatment period. No difference was found on BSS and PAC-QOL between two groups. Conclusion. It is effective and safe with EA to treat FC. Studies with large sample size and long-term observation are needed for further investigation.