Serum Zinc Ion Concentration Associated with Coronary Heart Disease: A Systematic Review and Meta-Analysis.

Aim: Coronary heart disease is a major cause of mortality in developed and developing countries. Changes in the trace element concentration in the human body are one of the main reasons for the transition of the human body from a healthy to a diseased state. In this meta-analysis, we have studied the relationship between the reduction in serum zinc ion concentration and coronary heart disease. Methods: We used PubMed and Cochrane (as of June 30, 2021) databases for the literature search. Per the requirements of this systematic review, case-control studies involving serum zinc ion concentration and coronary heart disease were searched, and the quality of the included studies was evaluated before the meta-analysis. Results: A total of 3,981 cases were found across seven articles. The standard mean deviation (SMD) of serum zinc ion concentration was -0.22 [-0.28, -0.15], z = 6.52, and P < 0.05 indicated that the difference was statistically significant. The forest plot results show that I 2 = 34% < 50%, and the Q test showed P=0.17 > 0.1. These results suggest a lack of heterogeneity among the selected articles. Results from the funnel chart indicated that this study was free from publication bias. Conclusion: The results of this meta-analysis reveal that a decrease in serum zinc ion concentration is related to the occurrence of coronary heart disease. Clinically, monitoring the serum zinc ion levels is proven to be of great significance for patients with coronary heart disease.

Association of Low Expression of NUMB in Peripheral Blood with Acute Myocardial Infarction.

Objective: Our study's goal was to find out acute myocardial infarction (AMI) patients' NUMB gene expression patterns and to evaluate its role as a diagnostic marker for AMI detection. Methods: Peripheral blood was drawn from 124 individuals who had an AMI and 115 patients who had stable coronary artery disease (SCAD). The real-time quantitative polymerase chain reaction was used to measure the mRNA expression level of the NUMB gene in peripheral blood. Results: The AMI group's NUMB gene expression was 0.906 (0.181-0.954), whereas the SCAD group's expression was 1.024 (0.207-1.127). However, the AMI group had 0.885 times lower NUMB mRNA expression than the SCAD group (P < 0.05). Conclusion: Multivariate logistic regression evaluation found that lower NUMB expression was correlated with an increased risk of coronary artery disease. However, age and fasting plasma glucose levels were not associated with decreased NUMB expression.

Cardiovascular syphilis-associated acute myocardial infarction: A case report.

RATIONALE: In recent decades, the incidence of advanced syphilis has declined due to early recognition and the application of effective antibiotics. Advanced syphilis often manifests in the cardiovascular system as simple aortitis, aortic valve insufficiency, coronary artery stenosis or obstruction, Aortic aneurysm and mucinous myocarditis. In most case reports on the subject, acute myocardial infarction caused by syphilis was reported to be due to aortic valve insufficiency and coronary stenosis as a result of the involvement of the aorta. PATIENT CONCERNS: The patient was a 48-year-old woman. She was admitted to our hospital because of intermittent upper abdominal pain with chest tightness for 3 hours. The patient reported a past syphilis infection, when she was hospitalized for hysteromyoma surgery four years ago, and had no related treatment. DIAGNOSIS: According to the characteristics of coronary angiography and results of lab tests and echocardiography, she was finally diagnosed with myocardial infarction associated with syphilis. INTERVENTIONS: At the first diagnosis of syphilis, the patient did not received antibiotics treatment. After the diagnosis of myocardial infarction, she received the percutaneous coronary intervention (PCI) operation assisted by extracorporeal membrane oxygenation (ECMO) technology, successfully got drug -eluted stents in right coronary artery ostium and left main ostium. Then the patient received penicillin to treat the syphilis infection. OUTCOMES: After coronary revascularization, the cardiac function of the patients was gradually improved, and the left ventricular ejection fraction was gradually improved after combined with optimized drug therapy. LESSONS: The cardiovascular system is often involved in the stages of advanced syphilis with severe complications like myocardial infarction. Standard treatment should be given as soon as syphilis is diagnosis. For stenosis of coronary ostium, the PCI assisted by ECMO technology did not only ensure the effectiveness of the treatment, but also reduce the surgical risk of the patient. This case indicated the effectiveness of ECMO-assisted PCI, and thus may provide a reference for future patient treatment.

A novel nonsense mutation in TNNT2 in a Chinese pedigree with hypertrophic cardiomyopathy: A case report.

RATIONALE: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease and a common cause of sudden cardiac death, heart failure, atrial fibrillation and stroke. In families affected by HCM, genotyping is useful for identifying susceptible relatives. In the present study, we investigated the disease-causing mutations in a three-generation Chinese family with HCM using whole exome sequencing (WES). PATIENT CONCERNS: The proband, a 50-year-old man, was diagnosed with HCM at the age of 41 years. He presented with an asymmetric hypertrophic interventricular septum and a maximum interventricular septum thickness of 18.04 mm. His third elder sister, niece and daughter were also clinically affected by HCM. DIAGNOSIS: Autosomal dominant HCM. INTERVENTIONS: Seven family members, including 4 affected members, accepted WES. The genetic variants were subsequently called using Genome Analysis Toolkit and annotated using the InterVar program. Following frequency filtration by the Genome Aggregation Database, the variants were evaluated using an in-house bioinformatics analysis pipeline. OUTCOMES: HCM was transmitted as an autosomal dominant trait in the family. An extremely rare stop gained mutation, rs796925245 (g.1:201359630G>A, c.835C>T, p.Gln279Ter) in the troponin T2 (TNNT2) gene was identified as the disease-causing mutation. The stop gained mutation was predicted to result in a truncated troponin T protein in cardiac sarcomere. An adolescent family member who had normal echocardiographic measurements was found to carry the same disease-causing mutation. LESSONS: A novel nonsense TNNT2 mutation was identified as the HCM-causing mutation in this Chinese pedigree. Since HCM shows a low penetrance by clinical criteria in adolescents, the adolescent mutation carrier, who is still clinically unaffected, should be offered routine follow-ups and sport activity recommendations to prevent adverse events including sudden cardiac death in the future.

MicroRNA-34c suppresses proliferation of vascular smooth muscle cell via modulating high mobility group box protein 1.

BACKGROUND: Atherosclerosis is the most frequent pathological process that causes cardiovascular diseases. OBJECTIVE: The present study aimed to confirm miRNAs associated with atherosclerosis and explore the molecular mechanism of miR-34c and its target high mobility group box protein 1 (HMGB1) in the control of growth of smooth muscle cells in the development of atherosclerosis. METHODS: Real-time PCR was firstly performed to confirm miRNA correlation with atherosclerosis, and computational analysis and luciferase assay were performed to explore the target of miR-34c, Western blot, and real-time PCR were also utilized to reveal the effect of whether high glucose (HG) and miR-34c affect miR-34c, HMGB1 levels, NF-κB p65 and TNF-α levels, and the role of miR-34c on vascular smooth muscle cells (VSMCs) viability induced by HG. Students' unpaired t test was performed to compare data between two groups. RESULTS: MiR-34c level was associated with atherosclerosis with different expression between VSMCs treated with high glucose or normal VSMCs. Then, HMGB1 is a virtual target of miR-34c with predicted binding site resided in HMGB1 3'UTR and further verified by that miR-34c remarkably reduced luciferase activity of wild HMGB1 3'UTR under a concentration-dependent fashion, and miR-34c cannot influence luciferase activity of mutant HMGB1 3'UTR. CONCLUSIONS: The results suggested miR-34c might be a novel therapeutic strategy in the management of atherosclerosis by suppressing the expression of HGMB1 and its downstream effectors.

Role of epigenetic in leukemia: From mechanism to therapy.

Epigenetic variations can play remarkable roles in different normal and abnormal situations. Such variations have been shown to have a direct role in the pathogenesis of various diseases either through inhibition of tumor suppressor genes or increasing the expression of oncogenes. Enzymes involving in epigenetic machinery are the main actors in tuning the epigenetic-based controls on gene expressions. Aberrant expression of these enzymes can trigger big chaos in the cellular gene expression networks and finally lead to cancer progression. This situation has been shown in different types of leukemia, where high or low levels of an epigenetic enzyme are partly or highly responsible for the involvement or progression of a disease. DNA hypermethylation, different histone modifications, and aberrant miRNA expressions are three main epigenetic variations, which have been shown to play a role in leukemia progression. Epigenetic based treatments now are considered as novel and effective therapies in order to decrease the abnormal epigenetic modifications in patient cells. Different epigenetic-based approaches have been developed and tested to inhibit or reverse the unusual expression of epigenetic agents in leukemia. Acute myeloid leukemia (AML), the most prevalent acute leukemia in adults, is anaggressive hematological malignancy arising in hematopoietic stem and progenitor cells. With the exception of a few specific AML subtypes, the mainstays of treatment have not significantly changed over the last 20 years, and are still based on standard cytotoxic chemotherapy. In this review, we will discuss the recent development of therapeutics specifically targeting these key epigenetic programs in AML, describe their mechanism of action and present their current clinical development. Finally, we will discuss the opportunities presented by epigenetically targeted therapy in AML and will highlight future challenges ahead for the AML community, to ensure that this novel therapeutics are optimally translated into clinical practice and result in clinical improvement for AML patients.

Vascular Risk Factors and Alzheimer's Disease: Blood-Brain Barrier Disruption, Metabolic Syndromes, and Molecular Links.

Alzheimer's disease (AD) is a neurodegenerative disorder, marked by cortical and hippocampal deposition of amyloid-ß (Aß) plaques and neurofibrillary tangles and cognitive impairment. Studies indicate a prominent link between cerebrovascular abnormalities and the onset and progression of AD, where blood-brain barrier (BBB) dysfunction and metabolic disorders play key risk factors. Pericyte degeneration, endothelial cell damage, astrocyte depolarization, diminished tight junction integrity, and basement membrane disarray trigger BBB damage. Subsequently, the altered expression of low-density lipoprotein receptor-related protein 1 and receptor for advanced glycation end products at the microvascular endothelial cells dysregulate Aß transport across the BBB. White matter lesions and microhemorrhages, dyslipidemia, altered brain insulin signaling, and insulin resistance contribute to tau and Aß pathogenesis, and oxidative stress, mitochondrial damage, inflammation, and hypoperfusion serve as mechanistic links between pathophysiological features of AD and ischemia. Deregulated calcium homeostasis, voltage gated calcium channel functioning, and protein kinase C signaling are also common mechanisms for both AD pathogenesis and cerebrovascular abnormalities. Additionally, APOE polymorphic alleles that characterize impaired cerebrovascular integrity function as primary genetic determinants of AD. Overall, the current review enlightens key vascular risk factors for AD and underscores pathophysiologic relationship between AD and vascular dysfunction.

Role of hydrogen sulfide in cognitive deficits: Evidences and mechanisms.

Hydrogen sulfide (H2S) is a gaseous molecule and is endogenously produced in the brain by cystathionine beta-synthase, 3-mercaptopyruvate-sulfurtransferase, cysteine aminotransferase and cystathionine γ-lyase. Physiologically, H2S acts as a neuromodulator and regulates synaptic activity of neurons and glia to promote the development of long-term potentiation. A decrease in H2S levels in the brain and plasma has been directly correlated with the degree of severity of Alzheimer disease in patients. A large number of studies have shown a decrease in the H2S levels in experimental models of cognitive dysfunction and exogenous administration of sodium hydrosulfide (NaHS), a H2S donor, has been shown to prevent the development of memory deficits. The beneficial effects of H2S in different models has been ascribed to decrease in neuroinflammation, up-regulation of antioxidant defense, decrease in endoplasmic reticulum (ER) stress, inhibition of phosphatidylinositol 3-kinase (PI3-K)/Akt signaling, inhibition of mitogen activated protein (MAP) kinases, decrease in glutamate and normalization of NMDA receptors, inhibition of matrix metalloproteinases (MMPs), up-regulation of silent information regulator 1 (Sirt 1) and preservation of mitochondrial function. The present review describes the role of H2S in different models of cognitive deficits and human subjects along with possible mechanisms.

An investigation of the levels of vitamins A, D, and E in the serum of Chinese pregnant women.

BACKGROUND: Vitamins A, D (Vitamin D2 and vitamin D3) and E, play an important role during pregnancy. METHODS: Sera were collected from 1056 normal pregnant women, who were between 18 and 40 years old, at seven different hospitals in northeastern China. The levels of Vitamin A and E in the sera samples were detected using HPLC (High Performance Liquid Chromatography), and the level of vitamin D was measured by LC-MS (Liquid Chromatography-Mass Spectrometry). Data were analyzed using IBM SPSS Statistics 21. RESULTS: The mean levels of vitamin A, D and E in the 1056 sera samples were 0.39 mg/L (0.38-0.39), 20.44 µg/L (19.86-21.08) and 12.96 mg/L (12.70-13.25), respectively. The levels of vitamin A, D, and E deficiency were 17.05%, 0.19%, and 56.44%, respectively. The levels of vitamin A, D, and E of those between age 21 and 31 among the 1056 pregnant women were similar. The correlation of vitamin E and D was significant at the .01 level (two-tailed), and the correlation of vitamin A and age was significant at the .05 level (2-tailed). CONCLUSION: According to our finding, the levels of vitamin A, D, and E in the sera of pregnant women in northeastern China were affected by where they live and their age. Vitamin D deficiency was very serious, vitamin A deficiency was common, while vitamin E seems to be sufficient.

l-Carnitine and heart disease.

Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15-17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20-30years. Although ß-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these drugs. Search for alternatives identified endogenous cofactor l-carnitine, which is capable of promoting mitochondrial ß-oxidation towards a balanced cardiac energy metabolism. l-Carnitine facilitates transport of long-chain fatty acids into the mitochondrial matrix, triggering cardioprotective effects through reduced oxidative stress, inflammation and necrosis of cardiac myocytes. Additionally, l-carnitine regulates calcium influx, endothelial integrity, intracellular enzyme release and membrane phospholipid content for sustained cellular homeostasis. Carnitine depletion, characterized by reduced expression of "organic cation transporter-2" gene, is a metabolic and autosomal recessive disorder that also frequently associates with CVD. Hence, exogenous carnitine administration through dietary and intravenous routes serves as a suitable protective strategy against ventricular dysfunction, ischemia-reperfusion injury, cardiac arrhythmia and toxic myocardial injury that prominently mark CVD. Additionally, carnitine reduces hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, etc. that enhance cardiovascular pathology. These favorable effects of l-carnitine have been evident in infants, juvenile, young, adult and aged patients of sudden and chronic heart failure as well. This review describes the mechanism of action, metabolism and pharmacokinetics of l-carnitine. It specifically emphasizes upon the beneficial role of l-carnitine in cardiomyopathy.

Effects of the Activin A-Follistatin System on Myocardial Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway in Heart Failure.

BACKGROUND: A previous study suggested that activin A inhibited myocardial cell apoptosis. This study thus aimed to explore the effects of the activin A-follistatin system on myocardial cell apoptosis in heart failure (HF) rats in order to determine whether or not the mechanism operates through the endoplasmic reticulum stress (ERS) pathway. METHODS: Myocardial infarction (MI) by vascular deprivation was used to induce HF. The enzyme-linked immunosorbent assay was used to detect activin A, follistatin and brain natriuretic peptide (BNP) contents in serum. Immunohistochemical staining for activin A, follistatin, CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP) and caspase-3 was performed on the myocardial tissue. The activin A-stimulated apoptosis of H9c2 cells was tested by flow cytometry. Western blot was used to detect the expression levels of activin A, follistatin and ERS-related proteins. RESULTS: It was found that the high expression of activin A could cause activin A-follistatin system imbalance, inducing myocardial cell apoptosis via ERS in vivo. When HF developed to a certain stage, the expression of follistatin was upregulated to antagonize the expression of activin A. Activin A inhibited cardiomyocyte apoptosis with a low concentration and promoted apoptosis with a high concentration in vitro, also via ERS. CONCLUSION: Activin A-follistatin system participated in ERS-mediated myocardial cell apoptosis in HF.

Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2).

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression through the endogenous RNA interference machinery. Treatments with combination of chemotherapy with surgery are essential for advanced-stage colorectal cancer. However, the development of chemoresistance is a major obstacle for clinical application of anticancer drugs. In this study, we report a miR-203-SIK2 axis that involves in the regulation of Taxol sensitivity in colon cancer cells. MiR-203 is downregulated in human colon tumor specimens and cell lines compared with their normal counterparts. We report miR-203 is correlated with Taxol sensitivity: overexpression of miR-203 sensitizes colon cancer cells and the Taxol-resistant cells display downregulated miR-203 compared with Taxol-sensitive cells. We identify SIK2 as a direct target of miR-203 in colorectal cancer cells. Overexpression of miR-203 complementary pairs to the 3' untranslated region (UTR) of SIK2, leading to the sensitization of Taxol resistant cells. In addition, miR-203 and the salt-inducible kinase 2 (SIK2) are reverse expressed in human colorectal tumors. Finally, we demonstrate recovery of SIK2 by overexpression of SIK2-desensitized Taxol-resistant cells, supporting the miR-203-mediated sensitization to Taxol, is through the inhibition of SIK2. In general, our study will provide mechanisms of the microRNA-based anti-tumor therapy to develop anti-chemoresistance drugs.

Levocarnitine protects H9c2 rat cardiomyocytes from H2O2-induced mitochondrial dysfunction and apoptosis.

BACKGROUND: Although the protective effects of levocarnitine in patients with ischemic heart disease are related to the attenuation of oxidative stress injury, the exact mechanisms involved have yet to be fully understood. Our aim was to investigate the potential protective effects of levocarnitine pretreatment against oxidative stress in rat H9c2 cardiomyocytes. METHODS: Cardiomyocytes were exposed to H2O2 to create an oxidative stress model. The cells were pretreated with 50, 100, or 200 µM levocarnitine for 1 hour before H2O2 exposure. RESULTS: H2O2 exposure led to significant activation of oxidative stress in the cells, characterized by reduced viability, increased intracellular reactive oxygen species, lipid peroxidation, and reduced intracellular antioxidant activity. Mitochondrial dysfunction was also observed following H2O2 exposure, reflected by the loss of mitochondrial transmembrane potential and intracellular adenosine triphosphate. These pathophysiological processes led to cardiomyocyte apoptosis through activation of the intrinsic apoptotic pathway. More importantly, the levocarnitine pretreatment attenuated the H2O2-induced oxidative injury significantly, preserved mitochondrial function, and partially prevented cardiomyocyte apoptosis during the oxidative stress reaction. Western blotting analyses suggested that levocarnitine pretreatment increased plasma protein levels of Bcl-2, reduced Bax, and attenuated cytochrome C leakage from the mitochondria in the cells. CONCLUSION: Our in vitro study indicated that levocarnitine pretreatment may protect cardiomyocytes from oxidative stress-related damage.

Glycyrrhizin improves p75NTR-associated sciatic nerve regeneration in a BALB/c mouse model.

Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Marsland, Glees and Erikson's silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.