Echinacoside inhibited cardiomyocyte pyroptosis and improved heart function of HF rats induced by isoproterenol via suppressing NADPH/ROS/ER stress.

Prevalence of heart failure (HF) continues to rise over time and is a global difficult problem; new drug targets are urgently needed. In recent years, pyroptosis is confirmed to promote cardiac remodelling and HF. Echinacoside (ECH) is a natural phenylethanoid glycoside and is the major active component of traditional Chinese medicine Cistanches Herba, which is reported to possess powerful anti-oxidation and anti-inflammatory effects. In addition, we previously reported that ECH reversed cardiac remodelling and improved heart function, but the effect of ECH on pyroptosis has not been studied. So, we investigated the effects of ECH on cardiomyocyte pyroptosis and the underlying mechanisms. In vivo, we established HF rat models induced by isoproterenol (ISO) and pre-treated with ECH. Indexes of heart function, pyroptotic marker proteins, ROS levels, and the expressions of NOX2, NOX4 and ER stress were measured. In vitro, primary cardiomyocytes of neonatal rats were treated with ISO and ECH; ASC speckles and caspase-1 mediated pyroptosis in cardiomyocytes were detected. Hoechst/PI staining was also used to evaluate pyroptosis. ROS levels, pyroptotic marker proteins, NOX2, NOX4 and ER stress levels were all tested. In vivo, we found that ECH effectively inhibited pyroptosis, down-regulated NOX2 and NOX4, decreased ROS levels, suppressed ER stress and improved heart function. In vitro, ECH reduced cardiomyocyte pyroptosis and suppressed NADPH/ROS/ER stress. We concluded that ECH inhibited cardiomyocyte pyroptosis and improved heart function via suppressing NADPH/ROS/ER stress.

[Randomized controlled trial of internal heat-type acupuncture needle therapy in the treatment of post-stroke shoulder pain].

OBJECTIVE: To evaluate the effectiveness and safety of internal heat-type acupuncture needle (IHTAN) the-rapy in the treatment of post-stroke shoulder pain in apopletic patients. METHODS: According to the random number table, 96 patients with post-stroke shoulder pain were divided into IHTAN group and warm needle moxibustion group (n＝48 in each one). Jianyu (LI15), Jianliao (TE14), Jianzhen (SI9), Binao (LI14) and Ashi points (Extra) on the affected side were selected in the two groups. For patients of the IHTAN group, internal warmth controllable acupuncture needles were inserted into the above-mentioned acupoints, and then connected to an internal heat acupuncture apparatus for stimulating the acupoints at 42 ℃， 20 min every time, once a week, for 4 weeks. For patients of the warm needle moxibustion group, the above mentioned acupoints were stimulated with filiform needles attached with an ignited moxa-stick, once every other day, for 4 weeks. If the shoulder pain disappeared or basically disappeared, it was considered to be healed, if the pain was relieved, it was considered to be effective, ot-herwise, it was considered to be ineffective. The incidence of local skin injury including burn, empyrosis, silt blue, hematoma and infection, the heart rate, respiration, blood pressure, oxyhemoglobin saturation, blood routine (hemoglobin level, white blood cell [WBC] count, platelet count), creatase and dipolymer levels were recorded or detected. Additionally, the patients' satisfaction rate about the treatment environment was recorded. RESULTS: Following the treatment, of the 45 and 47 cases in the warm needle moxibustion and IHTAN groups, 5 (11.11%) and 20 (42.55%) were cured, 26(57.78%) and 21(44.68%) experienced marked improvement, and 14 (31.11%) and 6 (12.77%) had no apparent changes in their shoulder pain severity, with the total effective rates being 68.89% and 87.23%, respectively. The curative rate and total effective rate of the IHTAN group were significantly higher than those of the warm needle moxibustion group (P<0.01，P<0.05). The incidence of skin injury of the IHTAN group was evidently lower than that of the warm needle moxibustion group (P<0.01), and the patients' therapeutic environment satisfaction rate was remarkably higher in the IHTNA group than in the warm needle moxibustion group (P<0.05). No significant differences were found between the two groups and between pre- and post-treatment in each group in the heart rate, respiration frequency, systolic and diastolic pressures, oxyhemoglobin saturation, hemoglobin content, WBC count, platelet count, and plasma dipolymer, creatine kinase, lactic dehydrogenase, and beta-hydroxybutyrate dehydrogenase levels (P>0.05). CONCLUSION: The IHTAN therapy is effective, safe and reliable in the treatment of post-stroke shoulder pain. In terms of the incidence of skin injury and the satisfaction degree of therapeutic environment, the internal heat-type acupuncture needle therapy is obviously superior to the warm needle moxibustion therapy.

[Short-term and long-term therapeutic effects of internal heat-type acupuncture needle therapy combined with acupoint injection of O3 for post-stroke shoulder pain].

OBJECTIVE: To observe the short-term and long-term therapeutic effects of internal heat-type acupuncture needle (IHTAN) therapy combined with acupoint injection of O3for post-stroke shoulder pain in apopletic patients. METHODS: Patients with post-stroke shoulder pain were divided into warm needle moxibustion ＋ acupoint injection group (29 cases), acupoint injection group (30 cases) and IHTAN＋acupoint injection group (29 cases) according to the random number table. For acupoint injection, O3 solution (3 mL, 30 µg/mL) was injected into Jianyu (LI15), Jianliao (SJ14), Jianzhen (LI9), Binao (LI14) and Ashi points (4-6 acupoints every time) on the affected side, once every other day for 4 weeks. For warm needle moxibustion, the above mentioned acupoints were stimulated with filiform needles attached with an ignited moxa-stick, once every other day for 4 weeks. For IHTAN, the internal warmth controllable acupuncture needles were inserted into the above mentioned acupoints on the affected side, and then connected to an internal heat acupuncture apparatus for stimulating the acupoints at 42 ℃， 20 min every time, once a week, for 4 weeks. The severity of shoulder pain was assessed by using visual analogue scale (VAS, 0-10 points), the upper limb joint motion function evaluated using Fugl-Meyer assessment scale (FMA, 0－66 points), and the ability of daily living activities (ADL) evaluated using Barthel index (0－100 points) at the ends of the 2nd and 4th week as well as the 6th month after the treatment. If the shoulder pain disappeared or basically disappeared, it was considered to be healed. If the pain was relieved, it was considered to be effective. Otherwise, it was considered to be ineffective. RESULTS: At the ends of the 2nd and 4th week as well as the 6th month after the treatment, the VAS scores of the IHTAN＋acupoint injection group were significantly lower than those of the warm needle moxibustion＋acupoint injection and acupoint injection groups (P<0.05), and the FMA and ADL scores were significantly higher in the IHTAN＋acupoint injection group than in the other two groups (P<0.05). No significant differences were found between the warm needle moxibustion＋acupoint injection and the acupoint injection groups in the scores of VAS, FMA and ADL (P>0.05). Of the 29, 30 and 29 cases in the warm needle moxibustion＋acupoint injection, acupoint injection and IHTNA＋acupoint injection groups, 1, 0 and 7 cases at the 2nd week, 3, 2 and 12 cases at the 4th week, 4, 2 and 15 cases at the 6th month were cured; 15, 14 and 16 cases at the 2nd week, 17, 17 and 13 cases at the 4th week, and 18, 18 and 12 cases at the 6th month experienced marked improvement; 13, 16 and 6 cases at the 2nd week, 9, 11 and 4 cases at the 4th week, 7, 10 and 2 cases at the 6th month had no apparent changes in their shoulder pain severity, with the total effective rates at the 4th week and 6th month being 68.97% and 75.86%, 63.33% and 66.60%, and 86.21% and 93.10%, respectively. CONCLUSION: The internal heat-type acupuncture needle therapy combined with O3 acupoint injection has obvious short-term and long-term therapeutic effects for post-stroke shoulder pain and is obviously superior to warm needle moxibustion＋ acupoint injection and simple acupoint injection in relieving shoulder pain and improving upper limb motion function.

High-fat diet induces dynamic metabolic alterations in multiple biological matrices of rats.

Obesity is a condition resulting from the interactions of individual biology and environmental factors causing multiple complications. To understand the system's metabolic changes associated with the obesity development and progression, we systematically analyzed the dynamic metabonomic changes induced by a high-fat diet (HFD) in multiple biological matrices of rats using NMR and GC-FID/MS techniques. Clinical chemistry and histopathological data were obtained as complementary information. We found that HFD intakes caused systematic metabolic changes in blood plasma, liver, and urine samples involving multiple metabolic pathways including glycolysis, TCA cycle, and gut microbiota functions together with the metabolisms of fatty acids, amino acids, choline, B-vitamins, purines, and pyrimidines. The HFD-induced metabolic variations were detectable in rat urine a week after HFD intake and showed clear dependence on the intake duration. B-vitamins and gut microbiota played important roles in the obesity development and progression together with changes in TCA cycle intermediates (citrate, α-ketoglutarate, succinate, and fumarate). 83-day HFD intakes caused significant metabolic alterations in rat liver highlighted with the enhancements in lipogenesis, lipid accumulation and lipid oxidation, suppression of glycolysis, up-regulation of gluconeogenesis and glycogenesis together with altered metabolisms of choline, amino acids and nucleotides. HFD intakes reduced the PUFA-to-MUFA ratio in both plasma and liver, indicating the HFD-induced oxidative stress. These findings provided essential biochemistry information about the dynamic metabolic responses to the development and progression of HFD-induced obesity. This study also demonstrated the combined metabonomic analysis of multiple biological matrices as a powerful approach for understanding the molecular basis of pathogenesis and disease progression.