Effect of preinitiated glucose-insulin-potassium strategy for patients with undergoing planned percutaneous coronary intervention: a systematic review and meta-analysis.

OBJECTIVES: Whether the glucose-insulin-potassium (GIK) should be used as an adjuvant therapy for ischaemic myocardial disease remains controversial nowadays reperfusion era. This meta-analysis aimed to assess the effects of preinitiated GIK for patients undergoing planned percutaneous coronary intervention (PCI). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of science, MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched through 27 November 2022. ELIGIBILITY CRITERIA: Only randomised controlled trials involving participants preinitiated with GIK or placebo before planned PCI were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used standardised methods to search, screen and code included trials. Risk of bias was assessed with the Cochrane tool. Pooled analysis was conducted using random or effects models according to the heterogeneity. Subgroup analyses were carried out for dosage of GIK and if with ongoing myocardial ischaemia. RESULTS: 13 randomised controlled trials (RCTs) including 3754 participants were evaluated. We found patients preconditioned with GIK before PCI showed a significant increase in Thrombolysis in Myocardial Infarction 3 flow events after angioplasty (OR 1.59, 95% CI 1.03 to 2.46, p=0.04), also revealed improved in-hospital left ventricular ejection fraction (weighed mean difference, WMD 1.62, 95% CI 0.21 to 3.03, p=0.02) and myocardial salvage index (WMD 0.09, 95% CI 0.01 to 0.16, p=0.03). Nevertheless, no benefit was observed in all-cause mortality neither on 30-day (OR 0.81, 95% CI 0.59 to 1.11, p=0.18) nor 6 months (OR 1.02, 95% CI 0.42 to 2.46, p=0.97). Furthermore, GIK intervention was associated with higher occurrences of complications such as phlebitis (OR 10.13, 95% CI 1.74 to 59.00, p=0.01) and hypoglycaemia (OR 10.43, 95% CI 1.32 to 82.29, p=0.03), but not hyperkalaemia (OR 9.36, 95% CI 0.50 to 175.27, p=0.13), liquid overload (OR 1.02, 95% CI 0.25 to 4.13, p=0.98) or in-hospital heart failure (OR 0.42, 95% CI 0.06 to 2.96, p=0.39). CONCLUSIONS: Our study shows preconditioning GIK exhibits myocardial reperfusion and cardiac function benefits for patients planning to receive PCI intervention, while also some complications such as phlebitis and hypoglycaemia accompany. PROSPERO REGISTRATION NUMBER: CRD42022326334.

Increased production of 8-oxo-7,8-dihydroguanine in human urine, a novel biomarker of osteoporosis.

Osteoporosis is a worldwide disease that seriously affects the quality of life and survival rate of the elderly. The detection of bone biomarkers will provide supplementary information on bone mineral density, contributing to the accurate diagnosis of osteoporosis and better health care for prevention. This study aimed to investigate the efficacy of oxidative stress markers-8-oxo-7,8-dihydroguanine (8-oxoGsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) in the assessment of osteoporosis. We conducted a cross-sectional study among menopausal women with a mean (standard deviation) age of 62.967 (7.798) years old (n = 151). Participants were recruited for the bone mineral density (BMD) assessment, blood and urinary samples. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-guanine concentrations were measured by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). The urinary 8-oxoGsn/Cre value differed significantly between normal and osteoporotic participants (p < 0.001), while the 8-oxodGsn/Cre value did not (p = 0.720). Even after adjusting for the age and body mass index, the BMD was still associated with urinary 8-oxoGsn/Cre value. ROC analysis showed that 8-oxoGsn has a strong diagnostic value for osteoporosis (AUC = 0.744). The results show for the first time that 8-oxoGsn may be a biomarker for the future diagnosis of osteoporosis in women.

Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

Arecoline excites the contraction of distal colonic smooth muscle strips in rats via the M3 receptor-extracellular Ca2+ influx - Ca2+ store release pathway.

Areca is a Chinese herbal medicine that is widely used for constipation. However the mechanisms of its action are not clear. We investigated the effects of arecoline, the most active component of areca, on the motility of rat distal colonic smooth muscle strips. In longitudinal muscle of distal colon (LMDC) and circular muscle of distal colon (CMDC), arecoline increased the contraction in a dose-dependent manner. Tetrodotoxin (TTX) did not inhibit the effects of arecoline. The contractile response to arecoline was completely antagonized by atropine. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) strongly depressed the response to arecoline, but gallamine and methoctramine did not. Nifedipine, 2-aminoethoxydiphenyl borate (2-APB), and Ca2+-free Krebs solution with EGTA partly inhibited the effects of arecoline. The sum of Ca2+-free Krebs solution, EGTA, and 2-APB completely inhibited the effects of arecoline. The results show that arecoline stimulates distal colonic contraction in rats via the muscarinic (M3) receptor - extracellular Ca2+ influx - Ca2+ store release pathway. It is likely that the action of areca in relieving constipation is due to its stimulation of muscle contraction.

Huang-Lian-Jie-Du-Tang inhibits myocardial remodeling in a rat model of metabolic syndrome.

Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese herbal medicine and a potential anti-inflammatory agent. HLJDT has been used successfully to treat inflammation in diabetic rats. The current study is aimed to evaluate the effectiveness of HLJDT on myocardial remodeling in a rat model of metabolic syndrome (MS). Twenty-one MS rats were divided into two groups: the MS group and the MS+HLJDT group. Ten Wister rats were a normal control group (NC group). HLJDT (1.04 g/100g) was orally administered daily for 12 weeks in the MS+HLJDT group. The trial lasted 12 weeks. Changes of echocardiography, histological staining, transmission electron microscope (TEM), and molecular biology examinations were made. After treatment, in the MS+HLJDT group, Masson staining and echocardiography data revealed decreased collagen fibers compared with the MS group. Messenger RNA levels of IL-6, ICAM-1, TNF-alpha, TGF-beta1, NF-kappaB in left ventricular tissues were lower than in the MS group, and volume of mitochondria and the phenotype of cardiac muscle cells in TEM were close to normal. The results suggested that HLJDT reduced myocardial collagen deposition and inhibited cardiac remodeling in a rat model of MS.

Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-gamma expression and suppressing NF-kappaB activity.

BACKGROUND: Tong-xin-luo capsule (TXL), used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats (SHR). METHODS: Sixteen eight-week-old SHRs were randomized into an SHR group (n = 8) and a TXL group (n = 8) that were given Tong-xin-luo capsule (1.5 mg x kg(-1) x d(-1)). Eight Wistar Kyoto (WKY) rats fed with 0.9% NaCl served as the control group (WKY group). Systolic blood pressure (BP), body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 (NF-kappaB P65) and peroxisome proliferators activated receptor gamma (PPAR-gamma) protein and phosphorylated inhibitor kappa alpha (IkappaBalpha) protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IkappaBalpha and NF-kappaB were measured by co-immunoprecipitation. PPAR-gamma mRNA, collagen I mRNA and collagen III mRNA were measured by real-time PCR. RESULTS: TXL inhibited NF-kappaB P65 expression and ventricular remodeling and suppressed the activation of NF-kappaB compared with the SHR group (P < 0.01, P < 0.05). TXL reduced IkappaBalpha phosphorylation, increased expression of PPAR-gamma protein and enhanced the physical interaction of the P65-P50 heterodimer with IkappaBalpha. The mRNA expression of PPAR-gamma was enhanced but the mRNA expression of collagen I mRNA and collagen I mRNA were suppressed by TXL. CONCLUSIONS: In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-gamma that could result in the inhibition of the activation of NF-kappaB.