miR828a-CsMYB114 Module Negatively Regulates the Biosynthesis of Theobromine in Camellia sinensis.

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.

Integrating network pharmacology and experimental models to identify notoginsenoside R1 ameliorates atherosclerosis by inhibiting macrophage NLRP3 inflammasome activation.

Atherosclerosis is a cardiovascular disease, accounting for the most common mortality cause worldwide. Notoginsenoside R1 (NGR1) is a characteristic saponin of Radix notoginseng that exhibits anti-inflammatory and antioxidant effects while modulating lipid metabolism. Evidence suggests that NGR1 exerts cardioprotective, neuroprotective, and anti-atherosclerosis effects. However, underlying NGR1 mechanisms alleviating atherosclerosis (AS) have not been examined. This study used a network pharmacology approach to construct the drug-target-disease correlation and protein-protein interaction (PPI) network of NGR1 and AS. Moreover, functional annotation and pathway enrichment analyses deciphered the critical biological processes and signaling pathways potentially regulated by NGR1. The protective effect of NGR1 against AS and the underlying mechanism(s) was assessed in an atherogenic apolipoprotein E-deficient (ApoE-/-) mice in vivo and an oxidized low-density lipoprotein (ox-LDL)-induced macrophage model in vitro. The network pharmacology and molecular docking analyses revealed that NGR1 protects against AS by targeting the NLRP3/caspase-1/IL-1ß pathway. NGR1 reduced foam cell formation in ox-LDL-induced macrophages and decreased atherosclerotic lesion formation, serum lipid metabolism, and inflammatory cytokines in AS mice in vivo. Therefore, NGR1 downregulates the NLRP3 inflammasome complex gene expression of NLRP3, caspase-1, ASC, IL-1ß, and IL-18, in vivo and in vitro.

Research Trends of Acupuncture Therapy on Chronic Pelvic Pain Syndrome from 2000 to 2022: A Bibliometric Analysis.

Background: Acupuncture is considered an important means of analgesic, which has been widely used in chronic pelvic pain syndrome (CPPS) management and treatment in recent years, published a large number of related documents. However, the relevant literature in this field has not been summarized and quantitatively analyzed. Therefore, this study aims to analyze the hotspots and predicting future research trends of acupuncture on pelvic pain syndrome. Methods: Search for the relevant publications of the web of science database from 2000 to 2022 about the treatment of acupuncture on chronic pelvic pain syndrome. The Citespace software and VosViewer software are used to analyze the visualization of the countries, institutions, authors, keywords and references and references in the literature. Results: A total of 173 publications were included. The annual number of essays gradually showed an overall growth trend over time. Medicine magazine is the most published journal in this field. J UROLOGY and Acupunct Med are the most cited journals and the most influential magazines; The most active and influential country is China, and the most produced institutions are Beijing University of Chinese Medicine; The most produced authors are Liu Zhishun. The most cited and most influential authors are Nickel JC and Armour M; keywords and cited reference analysis show that the quality of life, mechanism research, alternative medicine and electro-acupuncture will be the scientific hotspot of acupuncture treatment for chronic pelvic pain syndrome. Conclusion: This study shows that acupuncture on CPPS is increasingly valued and recognized. The future research hotspots will focus on the effects and mechanisms. In the future, more high-quality animal basic research will be required to explore the exact mechanism of acupuncture on CPPS. In addition, different parameters of acupuncture such as electric-acupuncture, stimulating frequency, duration and strength are also the focus of future research. More clinical trials are required to verify its safety and effectiveness.

Effectiveness and safety of music therapy for insomnia disorder patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Music therapy has been widely used clinically to relieve insomnia disorder patients. However, the efficacy of music therapy in the treatment of insomnia disorder patients is uncertain. The purpose of this study is to determine the effectiveness and safety of music therapy in the treatment of insomnia disorder patients. METHODS: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, China Biomedical Literature Database, and search-related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. RESULTS: This study will evaluate the current status of music therapy treatment for insomnia disorder patients, aiming to illustrate the effectiveness and safety of music therapy treatment. CONCLUSION: This study will provide a basis for judging whether music therapy is effective in treating insomnia disorder patients. INPLASY REGISTRATION NUMBER: INPLASY202150087.

Effectiveness and safety of music-supported therapy on mood in post-stroke rehabilitation patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Music-supported therapy has been widely used clinically to relieve post-stroke rehabilitation. However, the efficacy of Music-supported therapy in the treatment of Mood in post-stroke rehabilitation Patients is uncertain. The purpose of this study is to determine the effectiveness and safety of Music-supported therapy in the treatment of Mood in post-stroke rehabilitation Patients. METHODS: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, China Biomedical Literature Database, and search related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. RESULTS: This study will evaluate the current status of Music-supported therapy treatment for mood in post-stroke rehabilitation Patients, aiming to illustrate the effectiveness and safety of Music-supported therapy treatment. CONCLUSION: This study will provide a basis for judging whether Music-supported therapy is effective in treating mood in post-stroke rehabilitation Patients. INPLASY REGISTRATION NUMBER: INPLASY202120011.

Effectiveness and safety of acupuncture in the treatment of chronic severe functional constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupuncture has been widely used clinically to relieve chronic severe constipation. However, the efficacy of acupuncture in the treatment of chronic severe constipation is uncertain. The purpose of this study is to determine the effectiveness and safety of acupuncture in the treatment of chronic severe constipation. METHODS: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science, and Technology Journal Database, China Biomedical Literature Database, and search related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. RESULTS: This study will evaluate the current status of acupuncture treatment for chronic severe constipation, aiming to illustrate the effectiveness and safety of acupuncture treatment. CONCLUSION: This study will provide a basis for judging whether acupotomy is effective in treating chronic severe constipation. INPLASY REGISTRATION NUMBER: INPLASY202070002.

[Medicinal-powder-separated Long-snake Moxibustion over the Governor Vessel with Different Skin Vesiculation Conditions for Treatment of Patients with Rheumatoid Arthritis].

OBJECTIVE: To observe the curative effect of herbal-medicine -powder-separated "Long-snake moxibustion" over the Governor Vessel at different vesiculation conditions in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120 RA patients received herbal-powder-separated long-snake moxibustion in the present study and randomized into Banmao (Cantharides, CANT, being able to promote skin vesiculation for enhancing the therapeutic effect)-0 g group, CANT-1.5 g group and CANT-3.0 g group (n=40 in each group) according to the dosage of CANT used in the herbs-medicinal powder. In addition to Cantharides, the medicinal powder also contained Shexiang (Moschus, 1 g), Dingxiang (Flos Caryophylli,1 g) and Rougui (Cinnamon bark,1 g). When treated, the patient was asked to take a prone position, the ginger juice was evenly smeared on the patient's back from Dazhui (GV 14) to Yaoshu (GV 2, about 3 cm wide), then, the above-mentioned medicinal powder was spread on the smeared ginger juice, followed by putting a layer of gauze, ginger powder and ignited moxa-stick, respectively. The treatment was conducted once every 30 days, and twice altogether. The visual analog scale (VAS) was used to assess the pain seve-rity of moxibustion-induced skin vesiculation on the patient's back in 24 h after moxibustion. The severity of vesiculation was assessed according to the status of vesicles appeared at the local skin (0 point:no vesicles;3 points:string-of-beads-like vesicles with the vesicle diameter being less than 2 cm; 6 points:foliated vesicles with the vesicle diameter being larger than 2 cm). The patient's symptoms and dysfunction of hand-knee joints were scored, and serum rheumatoid factor (RF), C-reactive protein (CRP), immune globulin IgM and IgG contents were assayed by ELISA, and the erythrocyte sedimentation rate (ESR) was determined by using Westergren method. RESULTS: After moxibustion, of the three 40 RA patients in the CANT-0 g, CANT-1.5 g and CANT-3.0 g groups, 0, 10 and 12 cases were under control in their symptoms, 7, 16 and 19 experienced marked improvement, 17, 9 and 6 were improved, 16, 5 and 3 failed in the treatment, with the effective rates being 60.0%(16/40), 87.5%(35/40) and 92.5%(37/40), respectively. The curative effects of CANT-1.5 g and CANT-3.0 g were significantly superior to that of CANT-0 g (P<0.01). Both the scores for skin vesiculation status and pain severity were significantly higher in the CANT-3.0 g group than in the CANT-0 g (no skin vesiculation) and CANT-1.5 g groups, and markedly higher in the CANT-1.5 g group than in the CANT-0 g group (P<0.01). Following the treatment, the symptom score and joint dysfunction score, ESR level, and serum RF, CRP, IgM and IgG contents were considerably decreased in the three groups in comparison with pre-treatment in the same one group (P<0.01); and those of the CANT-1.5 g and CANT-3.0 g groups were markedly lower than those of CANT-0 g group (P<0.01). In addition, CANT-3.0 g was notably superior to CANT-1.5 g in lowering symptom and joint dysfunction scores, ESR, serum RF and CRP contents (P<0.05). No significant differences were found between the CANT-1.5 g and CANT-3.0 g groups in serum IgM and IgG levels and in the therapeutic effect (P>0.05). CONCLUSIONS: Long-snake moxibustion combined with CANT-induced vesiculation has a good curative effect in the treatment of RA, which may be associated with its effects in lo-wering ESR level, and serum RF, CRP, IgM and IgG contents. The curative effect of vesiculation moxibustion is far better than non-vesiculation moxibustion, but mild vesiculation moxibustion is recommended due to severe pain of CANT-3.0 g.

[Long-snake moxibustion for rheumatoid arthritis:a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy differences among long-snake moxibustion, warm needling and western medication on rheumatoid arthritis and explore its effect mechanism. METHODS: One hundred and twenty patients were randomized into a long-snake moxibustion group, a warm needling group and a western medication group, 40 cases in each one. In the long-snake moxibustion group, the long-snake moxibustion was used. The ginger-isolated moxibustion was applied along the governor vessel, from Dazhui (GV 14) to Yaoshu (GV 2), once a month, for 2 months. In the warm needling group, the main points included Dazhui (GV 14), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Zhiyang (GV 9), Mingmen (GV 4) and Yaoyangguan (GV 3). The warm needling technique was used at 4 to 5 points each time, and 3 moxa cones were required at each points. The treatment was given once every two days, for 2 months. In the western medication group, methotrexate was prescribed for oral administration, 10 mg each time, once a week. If the joint pain score or joint swelling score was up to 6, diclofenac sodium was combined, 25 mg each time, 3 times a day, for 2 months. The symptom score, physical sign score, the visual analogue scale (VAS) score, levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), immunoglobulin M (IgM) and immunoglobulin G (IgG) were observed before and after treatment in the patients of the three groups. RESULTS: The treatments relieved the symptoms and physical signs of rheumatoid arthritis and improved VAS score and the levels of serum RF, ESR, CRP, IgM and IgG in all of the three groups (all P<0.01). The efficacy in the long-snake moxibustion group was significantly better than that in the warm needling group and the western medication group (P<0.05, P<0.01). CONCLUSIONS: The long-snake moxibustion achieves the significant clinical efficacy on rheumatoid arthritis, better than warm needling therapy and methotrexate. This therapy much better reduces immune response and alleviates the sickness.