Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction.

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 ß, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION: LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Therapeutic Mechanism and Clinical Observation of Traditional Chinese Medicine Combined with Interventional Recanalization for Tubal Infertility.

To observe the clinical effect of traditional Chinese medicine (TCM) combined with interventional recanalization therapy in the treatment of tubal obstructive infertility, first, different treatment approaches were used on rabbits, and transmission electron microscopy (TEM) indicated that interventional recanalization combined with TCM can significantly ameliorate the pathological condition of the fallopian tube after treatment. Moreover, ELISA disclosed that the treatment could significantly reduce the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and increase the expression of interleukin-10 (IL-10), which demonstrated that TCM therapy can help against inflammation of the fallopian tubes. PCR array analysis revealed that BMP4, BMPR1A, SMAD2, SMAD3, SMAD4, and KLF10 expressions were upregulated, and SMAD7 expression was downregulated, proving that combined treatment could influence gene expression in the TGF-ß family and further regulate the secretion of proteins in SMADs. In addition, a clinical study recorded the fallopian tube patency rate of 165 patients after 12 months. The recanalization rates in the two groups were 81.9% and 53.1%, with the higher rates in the combined medicine enema group. All these findings implied that interventional recanalization combined with TCM preparation has a stronger effect. The mechanism probably involves effects on the expression of genes in the TGF-ß/SMAD and BMP/SMAD signaling pathways, with simultaneous regulation of inflammatory factors, thereby improving the ovarian environment and increasing pregnancy rates.

Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?

Nicotinamide adenine dinucleotide (NAD) is essential for cellular physiological processes, directly or indirectly affecting metabolism and gene expression. The decline of NAD+ levels in the heart is accompanied by aging, causing cardiac pathological remodeling and dysfunction. Niacinamide mononucleotide (NMN) has emerged as a precursor to alleviate age-related cardiac pathophysiological changes by improving cardiac NAD+ homeostasis. Preclinical trials on the efficacy and safety of intaking NMN have shown encouraging results, revealing a cardioprotective effect without significant side effects. Strategies for improving the effectiveness of NMN are also evolving. The present review aimed to summarize the potentials of NMN as a nutraceutical against cardiac aging and highlight the relationship between NMN supplementation and cardiac protection.

The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials.

BACKGROUND: The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial. METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg-Mazumdar correlation test. RESULTS: Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, - 2.12; 95% CI, - 3.40 to - 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, - 1.91; 95% CI, - 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, - 2.36; 95% CI, - 4.30 to - 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, - 0.20; 95% CI, - 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, - 2.403; 95% CI, - 3.992 to - 0.813; p < 0.001) and high intensity statins (SMD, - 1.727; 95% CI, - 2.746 to - 0.709; p < 0.001) decreased circulating CoQ10. Meta-regression showed that the effect of statin on decreasing circulating CoQ10 was not closely associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). CONCLUSIONS: Statin treatment decreased circulating CoQ10 but was not associated with the statin solution, intensity, or treatment time. The findings of this study provide a potential mechanism for statin-associated muscle symptoms (SAMS) and suggest that CoQ10 supplementation may be a promising complementary approach for SAMS.

Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials.

Background Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

Relation between serum calcium levels and mortality in patients with coronary artery disease.

OBJECTIVES: Calcium has a critical role in a spectrum of biological processes related to cardiovascular disease. This study aimed to evaluate associations of baseline serum calcium levels with both short-term and long-term outcomes in CAD patients. MATERIALS AND METHODS: 3109 consecutive patients with angiography confirmed CAD, admitted to West China hospital of Sichuan University between July 2008 and September 2012 were enrolled and were categorized into quartiles according to admission serum calcium to determine the association of serum calcium level with in-hospital and long-term mortality by multivariable Logistic and Cox regression analysis respectively. RESULTS: The admission serum calcium was normally distributed with a mean level of 2.20±0.15 mmol/L. A total of 259 deaths, including 58 in-hospital deaths, occurred during a mean follow-up of 20 months. Patients in the upper quartiles of serum calcium, as compared to the lowest quartile of serum calcium, were presented with lower in-hospital mortality [HR was 0.391 (95% CI: 0.188-0.812), 0.231(95% CI: 0.072-0.501) and 0.223 (95% CI: 0.093-0.534) for three upper quartiles versus lowest quartile respectively] and long-term mortality [HR was 0.614 (95% CI: 0.434-0.869), 0.476(95% CI: 0.294-0.698) and 0.553 (95% CI: 0.349-0.777) respectively]. Similar association between serum calcium and long-term mortality as showed in total cohort were also obtained when restricting analyses to subgroups: stable CAD patients, ACS patients and discharged patients. CONCLUSIONS: As a widely available clinical index, serum calcium was an independent predictor of both in-hospital and long-term mortality among CAD patients. Further studies are warranted to determine mechanisms and whether patients with hypocalcaemia could benefit from calcium supplement.

[Effects of Mongolian new medicine-â ¡ on cardiac functions, endoplasmic reticulum stress and apoptosis in congestive heart failure rats with dilated cardiomyopathy].

OBJECTIVE: To investigate the effects of Mongolian new medicine-Ⅱ oncardiac functions, myocardial pathology, endoplasmic reticulum stress and myocardial apoptosis in congestive heart failure with dilated cardiomyopathy in rats. METHODS: Thirty SD male rats were randomly dividedinto 3 groups(n=10):control group, dilated cardiomyopathy group (intraperitoneal injection of adriamycin 2 mg/kg body weight, 1 time/week, 4 weeks after treatment were observed for 4 weeks), Mongolian new medicine-Ⅱ group(intraperitoneal injection of adriamycin 2 mg/kg body weight, 1 time/week, 4 weeks after treatment, 30 mg/(kg·d)was given Mongolian new medicine-Ⅱ orally for 4 weeks). During the experiment, general conditions of rats were observed. After 8 weeks, these rats were killed after measurement of the cardiac function indexes by high frequency echocardiography. The morphological changes of myocardial tissues were observed by using HEstaining, VG staining and electron microscopic. The myocardial apoptosis was detected by TUNEL method and the expressions of endoplasmic reticulum chaperone GRP78, GRP94, pro-apoptotic factor CHOP and caspase-3 were monitored by Western blot. RESULTS: ① Compared with dilated cardiomyopathy group, the cardiac systolic and diastolic functions were significantly increased in Mongolian new medicine-Ⅱ group, which were reflected in that left ventricular contraction diameter(LVIDs) and left ventricular end-diastolic diameter(LVIDd) were decreased, and left ventricular shortening fraction(FS) and ejection fraction(EF) were increased. The hemodynamic parameters of rats were improved significantly in Mongolian new medicine-Ⅱ group. ②Compared with dilated cardiomyopathy group, the myocardial lesion score was decreased and fibrosis of tissue space was relieved in Mongolian new medicine-Ⅱ group. ③Compared with dilated cardiomyopathy group, the apoptosis of myocardial cells was decreased. ④The expressions of endoplasmic reticulum chaperone GRP78, GRP94, pro-apoptotic factor chop and caspase-3 were decreased in Mongolian new medicine-Ⅱ group. CONCLUSIONS: Mongolian new medicine-Ⅱ could improve the pathologic alterations of cardiac cells and cardiac functions, decrease endoplasmic reticulum stress, the degree of fibrosis and myocardial apoptosis. The experimental results may be one of the mechanisms of treatment function of Mongolian new medicine-Ⅱ on dilated cardiomyopathy.

[The effect of astragalus injection on the expression of endoplasmic reticulum stress chaperonin GRP78 and GRP94 mRNA in adriamycin-injured cardiomyocytes with calumenin silencing by shRNA].

OBJECTIVE: To investigate the effect of astragalus injection on the endoplasmic reticulum stress in adriamycin(ADR)-injured cardiomyocytes with calumenin silencing by shRNA. METHODS: Firstly, the stable lentiviral calumenin shRNAvector was constructed. Secondly, in vitro cultured neonatal rat cardiac myocytes were randomly divided into control group、normal group (3 mg/L ADR), lentivirus infection group (lentivirus infection+3 mg/L ADR), Astragalus group 1 (3 mg/L ADR+Astragalus), Astragalus group 2 (lentivirus infection+3 mg/L ADR+Astragalus). The mRNA epression level of calumenin expression and reticulum stress chaperone in GRP78, GRP94 of each group was monitored by real-time PCR. RESULTS: ①Compared with that of the control group, the calumenin mRNA expression in the normal group was reduced(P<0.05), yet its mRNA level in lentivirus the infection group and the Astragalus group 2 was further reduced(P<0.01). Compared with that of the normal group, the mRNA contents of calumenin in the Astragalus group 1 was increased(P<0.05). The expression of calumenin in Astragalus group 2 was increased comparing with lentivirus infection group (P<0.01). ②Compared with that in the control group, the expression of reticulum stress chaperone in GRP78, GRP 94 in lentivirus infection group and normal group was significantly increased (P<0.01); Compared with that in the normal group, the expression of reticulum stress chaperone in GRP78, GRP94 in Astragalus group 1 was reduced(P<0.01); Compared with that in the lentivirus infection group, the expression of reticulum stress chaperone in GRP78, GRP94 in the Astragalus group 2 was obviously decreased(P<0.01). CONCLUSIONS: ①Calumenin can alleviate endoplasmic reticulum stress induced by ADR-injured myocardial cells. ②Astragalus injection can restrain the endoplasmic reticulum stress induced by adriamycin, which may be achieved by the calumenin protein.

[Evaluation of therapeutic effect and safety for clinical randomized and controlled trials of treatment of acne with acupuncture and moxibustion].

OBJECTIVE: To evaluate the therapeutic effect and safety of acupuncture and moxibustion for treatment of acne, and to analyze the current situation of clinical studies at present. METHODS: Retrieve PubMed, Cochrane library, CBM databank, CNKI databank, etc., and collect the randomized and controlled trials of treatment of acne with acupuncture and moxibustion, and select clinical trials conforming with the enrolled criteria, and conduct evaluation of quality with Cochrane systematic manual 5.0, and RevMan 4.2.8 was used for statistical analysis. RESULTS: Seventeen papers, including 1,613 cases, conformed with the enrolled criteria. Seventeen studies adopted the cured rate as the evaluation index, Meta-analysis showed treatment of acne by acupuncture and moxibustion with routine western medicine as control, significant difference for inter-group comparison [combined RR (random efficacy model) = 2.96, 95% CI (1.63, 4.91), Z=4.08. P<0.0001]; comprehensive acupuncture and moxibustion therapy was controlled with single acupuncture moxibustion therapy, significant difference for inter-group comparison [combined RR (fixed efficacy model) = 2.51, 95% CI (1.76, 3.57), Z=5.11, P<0.00001]. CONCLUSION: Acupuncture-mox ibustion is safe and effective for treatment of acne, and it is possibly better than routine western medicine, and the comprehensive acupuncture-moxibustion therapy is better than single acupuncture-moxibustion therapy. The conclusion has not been determined yet, because lower quality of a part of literature enrolled.