Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats. / 基于PI3K/Akt/mTORä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆæ²»ç–—åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM. METHODS: Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated. RESULTS: Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(P<0.01, P<0.05), while contents of PGE2 in the serum and uterine tissue were reduced(P<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(P<0.05, P<0.01), whereas the writhing latency was considerably prolonged in the EA group(P<0.01), with elevated contents of PGE2 in the serum and uterine tissue(P<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group. CONCLUSIONS: EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.

The relationship between attention networks and individual differences in visual mental imagery vividness - An EEG study.

Previous research has established a strong link between attention and visual mental imagery, but it's remained uncertain whether attention networks influence individual differences in the vividness of visual mental imagery. In our study, we examined 140 participants, assessing the vividness of imagery using the Vividness of Visual Imagery Questionnaire in both eyes-open and eyes-closed conditions. We employed the Attention Network Test, coupled with EEG recording, to characterize three attention sub-networks: alerting, orienting, and executive control. To pinpoint the specific attentional networks associated with the vividness of visual mental imagery, we utilized latent profile analysis to categorize participants into distinct subgroups. Additionally, we constructed a regression mixture model to explore how attention networks predict different latent categories of visual imagery vividness. Our findings revealed that the efficiency of the alerting network, as indicated by the N1 component, demonstrated a positive correlation with the vividness of visual imagery. This electrophysiological evidence underscores the role of the alerting network in shaping individual differences in the vividness of visual mental imagery.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

[Effects of electroacupuncture on N-methyl-D-aspartate receptor and mitogen activated protein kinase in spinal cord of rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on the expression levels of N-methyl-D-aspartate receptor (NMDAR), extracellular signal-regulated kinase (ERK)1/2, p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in the spinal cord of rats with primary dysmenoramia (PDM), so as to explore the underlying mechanism of EA treating PDM. METHODS: Thirty female SD rats were randomly divided into normal group, model group and EA group, with 10 rats in each group. The PDM rat model was established by subcutaneous injection of estradiol benzoate and oxytocin into the thigh. At the same time of modeling, rats in the EA group were treated with EA (50 Hz) at "Sanyinjiao" (SP36) and "Guanyuan" (CV4) once daily, 20 min each time, for 10 consecutive days. The writhing times, writhing score and writhing latency were observed within 30 min after oxytocin injection. The uterine pathological morphology was observed by HE staining, and pathological score was calculated. Serum prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) were determined by ELISA. The protein expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were detected by Western blot. RESULTS: Compared with the normal group, the writhing times and writhing score were significantly increased (P<0.05); the endometrial epithelial cells showed vacuolar degeneration, death and hyperemia, the uterine pathological score was increased (P<0.05); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly increased (P<0.01), while the content of serum PGE2 was significantly decreased (P<0.01); the expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were significantly increased (P<0.05, P<0.01) in the model group. Compared with the model group, the writhing times and writhing score were significantly decreased (P<0.05), the writhing latency was prolonged (P<0.05); the endometrial epithelial cells still showed vacuolar degeneration, death and hyperemia, and the uterine pathological score was decreased (P<0.01); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly decreased (P<0.01), while the content of serum PGE2 was significantly increased (P<0.01); the protein expression levels of ERK1/2 and JNK in spinal cord were significantly decreased (P<0.01) in the EA group. CONCLUSION: EA intervention at SP36 and GV4 has obvious analgesic effect on PDM rats, and its mechanisms may be related to reducing serum prostaglandin, alleviating uterine inflammation, and inhibiting the protein expressions of NMDAR, ERK1/2, p38 MAPK and JNK in spinal cord.

Electroacupuncture treatment of primary dysmenorrhea: A randomized, participant-blinded, sham-controlled clinical trial protocol.

BACKGROUND: Primary dysmenorrhea in women is a common and serious public health problem with psychological and physical effects. Painkillers have adverse effects, such as tolerance, addiction, irritation of the digestive tract, and liver and kidney damage. Electroacupuncture has been used as alternative therapy, although with no (non-anecdotal) evidence of effectiveness. OBJECTIVE: This study aims to provide evidence for the feasibility and efficacy of electroacupuncture in the treatment of primary dysmenorrhea. Moreover, by observing changes in serum and urine metabolites, we will evaluate the putative mechanisms mediating electroacupuncture effects in primary dysmenorrhea. METHODS: This multicenter, randomized, participant-blinded, sham-controlled clinical trial including 336 women with primary dysmenorrhea is being conducted at three hospital centers in China and consists of a 12-week treatment and a 3-month follow-up. Women will undergo electroacupuncture (n = 168) or sham acupuncture (n = 168), beginning 7 days before their menstruation, once per day, until menstruation. Each menstrual cycle equals one course of treatment, and we will evaluate a total of three courses of treatment. The primary outcome of interest is the change in visual analogue scale scores before and after treatment. The secondary outcomes include changes in the numeric rating scale, Cox Menstrual Symptom Scale, traditional Chinese medicine symptoms, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and 36-Item Short Form questionnaire scores, and a safety evaluation. Moreover, we will preliminarily investigate the metabolomics mechanism as a potential mediator of the association between electroacupuncture and primary dysmenorrhea symptomology. DISCUSSION: We aim to find a suitable non-medicinal alternative for primary dysmenorrhea treatment to reduce reliance on non-steroidal anti-inflammatory drugs. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100054234; http://www.chictr.org.cn/.

[Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years].

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, ß-amyloid(Aß), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

[Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM. METHODS: Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1ß, IL-18) in uterine tissue. RESULTS: In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05). CONCLUSION: EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

[Effect of electroacupuncture intervention on relieving pain and inflammation by suppressing TLR4/NF-κB signaling in rats with primary dysmenorrhea].

OBJECTIVE: To investigate the mechanism of electroacupuncture(EA) intervention in rats with primary dysmenorrhea(PDM) based on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB signaling pathway. METHODS: Forty female SD rats were randomly divided into blank control, model, EA and medication groups, with 10 rats in each group. PDM rat model was established by subcutaneous injection of estradiol benzoate combined with intraperitoneal injection of oxytocin. At the same time of model procedures, EA(50 Hz, dense wave) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao" (SP6) of rats in the EA group, with needles retained for 20 min, for 10 consecutive days. Rats in the medication group received ibuprofen(125 mg/100 mL, 0.8 mL) by gavage for 10 consecutive days. At the 11th day, writhing behavior of rats was assessed. Uterine morphology was observed by eyes and uterine pathological changes were observed after HE staining. Content of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in serum and uterine tissues was detected by ELISA; NF-κB p65 positive expression in nucleus was detected by immunofluorescence; protein expression levels of TLR4, NF-κB p65, p-NF-κB p65 and inflammatory factors interleukin (IL) -1ß and IL-18 were detected by Western blot. RESULTS: After modeling, uterus tissues were congested and edematous, with necrosis of luminal epithelium, severe edema and extensive shedding of endometrium, nuclear pyknosis, fragmentation and disappearance, neutrophils infiltration, and slight expansion of glandular cavity, which was milder in the EA and the medication groups. Compared with the blank control group, writhing times, scores and incubation period, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the model group were all significantly increased(P<0.01), while PGE2 contents in serum and uterine tissues were significantly decreased(P<0.01). Compared with the model group, writhing times and scores, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the EA and medication group were all significantly decreased(P<0.01), while writhing incubation period, PGE2 contents in serum and uterine tissues were significantly increased(P<0.05, P<0.01). CONCLUSION: EA intervention could relieve inflammatory response and pain in PDM rats, which may be related to its effect in reducing TLR4 expression, inhibiting NF-κB activation and down-regulating inflammatory factors levels of IL-1ß and IL-18.

Tongguanteng injection reverses paclitaxel resistance via upregulation of TAB1 expression in ovarian cancer in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mg⋅mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.

Vibsane-type diterpenoids from Viburnum odoratissimum inhibit hepatocellular carcinoma cells via the PI3K/AKT pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with an elevated danger of metastasis and a short survival rate. Vibsane-type diterpenoids with novel structures possess marked antitumor activities against multiple cancer cells. However, the exact mechanism is poorly unclear. PURPOSE: To assess the antitumor mechanism of vibsane-type diterpenoids derived from Viburnum odoratissimum (V. odoratissimum) against HCC cells in vitro and in vivo. METHODS: The main constituents in the ethyl acetate extract of V. odoratissimum (EAVO) were identified by LC-MS/MS. The antiproliferative activity of EAVO in vitro was evaluated by MTT assays. Annexin V-FITC/PI, AO/EB, and Hoechst 33,258 staining were employed to detect apoptosis. JC-1 fluorescence dye was used to detect the mitochondrial membrane potential (MMP). The levels of intracellular ROS and mitochondrial superoxides were assessed by H2DCF-DA and MitoSox staining, respectively. The levels of oxidative stress were determined by ROS Green™ H2O2 probe, hydroxyphenyl fluorescein (HPF), and the C11 BODIPY 581/591 fluorescent probe. Transcriptomics was performed to investigate the antitumor mechanism of EAVO in HCC. The molecular mechanism by which EAVO suppressed HCC cells was verified by Western blot, RT-PCR, and HTRF® KinEASE™-STK S3 kits. The efficacy and safety of EAVO in vivo were evaluated using Hep3B xenograft models. RESULTS: Vibsane-type diterpenoids were the main constituents of EAVO by LC-MS/MS. EAVO suppressed proliferation, aggravated oxidative stress, and promoted apoptosis in HCC cells. Moreover, EAVO dramatically inhibited tumor growth in Hep3B xenograft models. Transcriptomics results indicated that EAVO inhibited HCC cell proliferation by regulating the PI3K/AKT pathway. Vibsanin B, vibsanol I, and vibsanin S isolated from EAVO was used to further verify the antitumor activity of vibsane-type diterpenoids subsequently. Interestingly, the kinase results showed that vibsanin B and vibsanol I exhibited vital AKT kinase inhibitory activities. CONCLUSIONS: Collectively, this study provided a comprehensive mechanism overview of vibsane-type diterpenoids against HCC cells in vitro and in vivo. It also laid a foundation for further antitumor investigation of vibsane-type diterpenoids in V. odoratissimum.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Multidimensional Pain Modulation by Acupuncture Analgesia: The Reward Effect of Acupuncture on Pain Relief.

Pain is an intrinsically unpleasant experience with features that protect an organism by promoting motivation and learning. Pain relief, a negative reinforcement of pain, is considered a reward and activates the brain's reward system. The reward circuit in the brain involves reward and pain. Acupuncture has a multidimensional and comprehensive regulating effect on chronic pain. However, the reward effect of acupuncture in relieving chronic pain and the mechanism of the brain reward circuit involved in acupuncture analgesia are not thoroughly studied. In this article, we have reviewed the definition of pain abnormalities and negative emotions in patients with chronic pain, the conceptual characteristics of analgesic reward, and the new progress in studying brain reward circuits and functions. Moreover, we have expounded on the critical clinical and scientific significance of studying the reward effect of acupuncture analgesia and related brain reward circuits, the pain mechanism obtained from human neuroimaging studies, and the survey results on the effects of acupuncture on reward/motivation circuits. Some viewpoints and suggestions on the reward effect of acupuncture analgesia and related reward circuits have been put forward to clarify the multidimensional characteristics and benign regulation of acupuncture analgesia. Studies on the reward effect of acupuncture in relieving chronic pain and the regulating effect of the brain reward loop on acupuncture analgesia help to deepen the clinical understanding of acupuncture analgesia, innovate the research concept of acupuncture analgesia, and provide help for further studies on the central mechanism of acupuncture in improving chronic pain in the future.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND: Dendrobium officinale is an herb of Traditional Chinese Medicine (TCM) commonly used for treating stomach diseases. One formula of Granule Dendrobii (GD) consists of Dendrobium officinale and American Ginseng (Radix Panacis quinquefolii), and is a potent TCM product in China. Whether treatment with GD can promote gastric acid secretion and alleviate gastric gland atrophy in chronic atrophic gastritis (CAG) requires verification. AIM: To determine the effect of GD treatment on CAG and its potential cellular mechanism. METHODS: A CAG model was induced by feeding rats N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 wk. After oral administration of low, moderate, and high doses of GD in CAG rats for 8 wk, its effects on body weight, gastric mucosa histology, mucosal atrophy, intestinal metaplasia, immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2, and hemoglobin and red blood cells were examined. RESULTS: The body weights of MNNG-induced CAG model rats before treatment (143.5 ± 14.26 g) were significantly lower than that of healthy rats (220.2 ± 31.20 g, P < 0.01). At the 8th week of treatment, the body weights of rats in the low-, moderate-, and high-dose groups of GD (220.1 ± 36.62 g) were significantly higher than those in the untreated group (173.3 ± 28.09 g, all P < 0.01). The level of inflammation in gastric tissue of the high-dose group (1.68 ± 0.54) was significantly reduced (P < 0.01) compared with that of the untreated group (3.00 ± 0.00, P < 0.05). The number and thickness of gastric glands in the high-dose group (31.50 ± 6.07/mm, 306.4 ± 49.32 µm) were significantly higher than those in the untreated group (26.86 ± 6.41/mm, 244.3 ± 51.82 µm, respectively, P < 0.01 and P < 0.05), indicating improved atrophy of gastric mucosa. The areas of intestinal metaplasia were significantly lower in the high-dose group (1.74% ± 1.13%), medium-dose group (1.81% ± 0.66%) and low-dose group (2.36% ± 1.08%) than in the untreated group (3.91% ± 0.96%, all P < 0.01). The expression of PCNA in high-dose group was significantly reduced compared with that in untreated group (P < 0.01). Hemoglobin level in the high-dose group (145.3 ± 5.90 g/L), medium-dose group (139.3 ± 5.71 g/L) and low-dose group (137.5 ± 7.56 g/L) was markedly increased compared with the untreated group (132.1 ± 7.76 g/L; P < 0.01 or P < 0.05). CONCLUSION: Treatment with GD for 8 wk demonstrate that GD is effective in the treatment of CAG in the MNNG model by improving the histopathology of gastric mucosa, reversing gastric atrophy and intestinal metaplasia, and alleviating gastric inflammation.

[Optimization of processing technology of braised Rehmanniae Radix based on multiple indexes and response surface technology and correlation between components and color].

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.

Icariin attenuates excessive alcohol consumption-induced susceptibility to atrial fibrillation through SIRT3 signaling.

Excessive alcohol consumption has long been identified as a risk factor for adverse atrial remodeling and atrial fibrillation (AF). Icariin is a principal active component from traditional Chinese medicine Herba Epimedii and has been demonstrated to exert potential antiarrhythmic effect. The present study was designed to evaluate the effect of icariin against alcohol-induced atrial remodeling and disruption of mitochondrial dynamics and furthermore, to elucidate the underlying mechanisms. Excessive alcohol-treated C57BL/6 J mice were infected with serotype 9 adeno-associated virus (AAV9) carrying mouse SIRT3 gene or negative control virus. Meanwhile, icariin (50 mg/kg/d) was administered to the animals in the presence or absence of AAV9 carrying SIRT3 shRNA. We noted that 8 weeks of icariin treatment effectively attenuated alcohol consumption-induced atrial structural and electrical remodeling as evidenced by reduced AF inducibility and reversed atrial electrical conduction pattern as well as atrial enlargement. Furthermore, icariin-treated group exhibited significantly enhanced atrial SIRT3-AMPK signaling, decreased atrial mitoSOX fluorescence and mitochondrial fission markers, elevated mitochondrial fusion markers (MFN1, MFN2) as well as NRF-1-Tfam-mediated mitochondrial biogenesis. Importantly, these beneficial effects were mimicked by SIRT3 overexpression while abolished by SIRT3 knockdown. These data revealed that targeting atrial SIRT3-AMPK signaling and preserving mitochondrial dynamics might serve as the novel therapeutic strategy against alcohol-induced AF genesis. Additionally, icariin ameliorated atrial remodeling and mitochondrial dysfunction by activating SIRT3-AMPK signaling, highlighting the use of icariin as a promising antiarrhythmic agent in this circumstance.

Moxibustion for Primary Dysmenorrhea: An Adjuvant Therapy for Pain Relief.

The latest spectrum of moxibustion disease shows that primary dysmenorrhea is a high-frequency symptom of moxibustion and that it is the dominant clinical disease. In the specific treatment methods, all types of moxibustion methods have been widely used, such as thermal, thunder fire, partitioned, and spreading moxibustion. Moxibustion plays a therapeutic role through its four mechanisms of action: heat, light, moxa smoke, and drug effects. The mechanism of moxibustion treatment for primary dysmenorrhea focuses on adjusting endocrine hormones, regulating immune function and neuro-related factors, and improving uterine microcirculation. In this study, based on the clinical evidence of different moxibustion methods for treating primary dysmenorrhea, the design model, intervention characteristics, and clinical outcomes were analyzed. Meanwhile, the brain effect mechanisms of different imaging methods were summarized from the perspective of neuroimaging. It was pointed out that the left anterior cingulate gyrus, left inferior parietal angular gyrus, and left superior gyrus may be the analgesic brain regions that regulate sensory, emotional, and cognitive aspects. Moreover, the neural circuits involved can be inferred: the frontal cortex-basal ganglia (the pea nucleus)-cerebral cortex, which mediates motivation and emotional drive, and the parietal lobe-basal ganglia-limbic lobe-frontal lobe, which is involved in neurotransmitter transport and emotional regulation and behavioral expression. There are still problems and deficiencies in studies on the mechanism of moxibustion treatment for primary dysmenorrhea. Studies should be strengthened on how moxibustion produces an effect. Attention should be paid to exploring how the spectrum range and peak in the light effect of moxibustion treat primary dysmenorrhea. Studies assessing the mechanisms of moxibustion treatment for primary dysmenorrhea should be conducted to provide an experimental basis and evidence-based medical evidence for clinical treatment.

Activation of PKG-CREB-KLF15 by melatonin attenuates Angiotensin II-induced vulnerability to atrial fibrillation via enhancing branched-chain amino acids catabolism.

Mitochondrial reactive oxygen species (ROS) damage and atrial remodeling serve as the crucial substrates for the genesis of atrial fibrillation (AF). Branched-chain amino acids (BCAAs) catabolic defect plays critical roles in multiple cardiovascular diseases. However, the alteration of atrial BCAA catabolism and its role in AF remain largely unknown. This study aimed to explore the role of BCAA catabolism in the pathogenesis of AF and to further evaluate the therapeutic effect of melatonin with a focus on protein kinase G (PKG)-cAMP response element binding protein (CREB)-Krüppel-like factor 15 (KLF15) signaling. We found that angiotensin II-treated atria exhibited significantly elevated BCAA level, reduced BCAA catabolic enzyme activity, increased AF vulnerability, aggravated atrial electrical and structural remodeling, and enhanced mitochondrial ROS damage. These deleterious effects were attenuated by melatonin co-administration while exacerbated by BCAA oral supplementation. Melatonin treatment ameliorated BCAA-induced atrial damage and reversed BCAA-induced down-regulation of atrial PKGIα expression, CREB phosphorylation as well as KLF15 expression. However, inhibition of PKG partly abolished melatonin-induced beneficial actions. In summary, these data demonstrated that atrial BCAA catabolic defect contributed to the pathogenesis of AF by aggravating tissue fibrosis and mitochondrial ROS damage. Melatonin treatment ameliorated Ang II-induced atrial structural as well as electrical remodeling by activating PKG-CREB-KLF15. The present study reveals additional mechanisms contributing to AF genesis and highlights the opportunity of a novel therapy for AF by targeting BCAA catabolism. Melatonin may serve as a potential therapeutic agent for AF intervention.

Gender differences in Damp-Heat Syndrome: A review.

Gender differences have important biological significance for medical research. In this study, a bias towards males was identified in animal experiments of Damp-Heat Syndrome in traditional Chinese medicine, as was first proposed by a data mining method. Combined with the correlation between Damp-Heat Syndrome in traditional Chinese medicine and Gender differences, it was considered that Gender-related factors have a significant influence on the development of Damp-Heat Syndrome in traditional Chinese medicine. However, most traditional Chinese medicine studies ignore the key significance of Gender-related factors. This study emphasises that the development of modern traditional Chinese medicine research needs to pay full attention to the biological significance of Gender-related factors and to apply this concept to the research on the Gender equivalence strategy in basic research and the practice of personalised medical diagnosis and clinical treatment.

Efficacy and safety of massage therapy for autism spectrum disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder with increasing incidence. At present, the global incidence of the disease is on the rise, and the cause is unknown. There is no specific treatment for this disease at present, mainly education and training. Traditional Chinese medicine treatment has a certain effect on the improvement of the symptoms of the disease. The treatment methods are mainly oral Chinese medicine and acupuncture, but children are often not easy to cooperate. As a safe and effective green therapy, massage is easy to be accepted by children. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating autism spectrum disorders: Wanfang and PubMed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to March 2021. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with autism spectrum disorders. The outcomes will include changes in autism spectrum disorder relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with autism spectrum disorders. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.