Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia.

BACKGROUND: Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model. METHODS: The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule­1 (sICAM-1). CONCLUSION: The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.

Pyrroloquinoline quinone delays inflammaging induced by TNF-α through the p16/p21 and Jagged1 signalling pathways.

Previous studies on the longevity effect of pyrroloquinoline quinine (PQQ) on nematode worms have revealed that PQQ can enhance the antioxidant capacity of nematode worms, thus extending the lifespan of the worms. The induction and development of cellular senescence are closely connected with inflammatory reactions. The aim of this study was to determine the effect of PQQ and ageing factors on senescent cells. To this end, we cultivated human embryonic lung fibroblasts in nutrient solution with or without tumour necrosis factor-alpha (TNF-α) to establish an inflammaging model in vitro. The cells were preincubated with or without PQQ to determine if PQQ had any anti-inflammaging effect. More senescent cells were detected with the addition of TNF-α than without (P < .01). The ratio of senescent cells to non-senescent cells in the TNF-α group was greater than that in the control group (P < .01). When cells were preincubated with PQQ prior to TNF-α treatment, there were fewer senescent cells than those in the control group, which was not pretreated with PQQ (P < .05). The same tendency was noted with regard to p21, p16, and Jagged1. In summary, we used TNF-α, a well-known pro-inflammatory cytokine associated with inflammaging, to establish an in vitro inflammaging model and provided evidence that PQQ delays TNF-α -induced cellular senescence and has anti-inflammaging properties.

Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

PURPOSE: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. METHODS: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. RESULTS: Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. CONCLUSION: Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.

A mechanistic investigation into non-infarcted brain injury induced by cerebral artery microemboli.

To establish a rat brain injury by non-infarction process model induced by cerebral artery microemboli which would be used to further explore the neural injury mechanisms of cerebral artery microemboli. Seventy-two Sprague-Dawley rats were randomly divided into the microemboli group and the sham group; 100 25-50 µm microemboli in 300 µl or the same amount of saline were injected into the left carotid artery, respectively. The severity of neuron damage was assessed 3 and 7 days after the operation, using haematoxylin-eosin (HE) staining and immunohistochemical staining for caspase-3. Immunohistochemical staining for CD11b and GFAP were used to quantitatively analyse hyperplasia and the activation of microglia and astrocytes. TNF-α expression was detected by using ELISA and the NF-κB expression was detected by employing Western blotting. The results of HE staining had shown that ischaemic infarct foci were not detected in either the microemboli group or sham group. Only a few apoptotic cells and a few cells with the positive expression of CD11b and GFAP were detected in the sham group. And compared with that of the sham group, the number of apoptotic cells and the positive expression of CD11b and GFAP in the microemboli group were significantly increased (P < 0.001). These parameters were also significantly increased 7 days after the operation compared to rats 3 days after surgery (P < 0.001). The expressions of TNF-α and NF-κB were significantly increased in the microemboli group (P < 0.001), and the increase of the expression of TNF-α and NF-κB on the 3 days was more significant compared to that of TNF-α and NF-κB on 7 days (P < 0.001). Injection of 25-50 µm microemboli at a dose of 100 microemboli in 300 µl into the carotid artery of rats did not result in cerebral infarction, but led to neuronal apoptosis, hyperplasia and activation of microglia and astrocytes. This leads us to conclude that TNF-α and NF-κB may play important roles in the pathogenesis of neuronal apoptosis induced by microemboli in the cerebral arteries.

Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China.

Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5-7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable.

Chinese expert consensus on assessment of cognitive impairment in the elderly.

Cognitive impairment is a term that refers to the impairment of one or more cognitive domains to varying degrees caused by a variety of reasons. It is under a high prevalence, many risk factors, complex etiology, and great harm to the elderly population. Early screening, diagnosis, and intervention for cognitive impairment in the elderly are of great importance. However, at present, the recognition rate of cognitive impairment for the elderly in China is low, the rate of missed diagnosis is high, and the evaluation is not standardized. This consensus integrates the commonly used cognitive function assessment scales in China and abroad, and aims to popularize the screening of cognitive impairment, standardize the evaluation methods and procedures of cognitive impairment in the elderly, and establish clinical diagnoses, interventions, and follow-up plans in a timely manner.

Chinese expert consensus on prevention and intervention for the elderly with malnutrition (2022).

Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-n-butyl phthalate (DBP).

BACKGROUND: We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) induces dysplasia of the kidney in newborn male offspring and renal fibrosis in adults. But the underlying mechanisms remain elusive. Fgf10/Fgfr2 and androgen receptor (AR) are known to be important for renal development. We therefore investigated whether these genes are involved in DBP-induced renal fibrosis. MATERIALS AND METHODS: Using Sprague-Dawley rats and rat renal proximal tubular cells (NRK52E), we determined the potential involvement of Fgf10, Fgfr2 and AR in DBP-induced renal fibrosis. RESULTS: We found that maternal exposure to DBP induces renal fibrosis in adult male offspring. A lower serum testosterone concentration and reduced expression of Fgf10, Fgfr2 and AR were detected in these animals. These was a trend toward lower expression of Fgf10, Fgfr2 and AR in NRK52E cells subjected to DBP exposure. Furthermore, higher expression levels of TGF-ß and α-SMA were observed in abnormal renal tissue and DBP-treated NRK52E cells. CONCLUSION: Our findings suggest the potential involvement of Fgf10/Fgfr2 and AR in renal fibrosis of adult male rat offspring induced by prenatal exposure to DBP. The anti-androgenic effects of DBP might play an important role in this pathological process.

Role of depression in secondary prevention of Chinese coronary heart disease patients receiving percutaneous coronary intervention.

INTRODUCTION: Coronary heart disease (CHD) patients who have undergone percutaneous coronary intervention (PCI) have higher rates of depression than the general population. However, few researchers have assessed the impact of depression on the secondary prevention of CHD in China. OBJECTIVE: The main purpose of this investigation was to explore the relationship between depression and secondary prevention of CHD in Chinese patients after PCI. METHODS: This descriptive, cross-sectional one-site study recruited both elective and emergency PCI patients one year after discharge. Data from 1934 patients were collected in the clinic using questionnaires and medical history records between August 2013 and September 2015. Depression was evaluated by the 9-item Patient Health Questionnaire. Secondary prevention of CHD was compared between depression and non-depression groups. RESULTS: We found that depression affected secondary prevention of CHD in the following aspects: lipid levels, blood glucose levels, smoking status, physical activity, BMI, and rates of medication use. CONCLUSIONS: Depressive patients with CHD are at increased risk of not achieving the lifestyle and risk factor control goals recommended in the 2006 AHA guidelines. Screening should focus on patients after PCI because treating depression can improve outcomes by improving secondary prevention of CHD.

Oxidative damage of copper chloride overload to the cultured rat astrocytes.

Disorders of copper metabolism are associated with neurological dysfunction including Wilson's disease (WD). WD is a autosomal recessive disorder caused by mutations in the ATP7B gene resulting in the inability of the hepatocytes to remove excess copper. Gradual copper accumulation causes damage to liver, brain and other organs manifesting in liver disease, neurological and psychiatric symptoms. Also scond copper-neurometaboic disorder: Menkes disease charaterized with mutated ATP7A gene, is ralated with abnormally neuroal transmission and synaptogenesis. Parkinson's disease and Alzheimer's disease both are refered to some degree of copper/iron metabolism changes. The precise mechanisms by which excess copper causes neurological damage remain to be elucidated. In this study, we aimed to investigate the influence of excessive amounts of Cu(2+) on the oxidative damage response and survival of primary astrocytes from newborn rats. Primary cultured rat astrocytes were divided into three groups: 30 µmol/L CuCl2, 100 µmol/L CuCl2 and control. At 12, 24, 48, 96 and 120 hours of CuCl2 intervention, cell viability, intracellular reduced glutathione level and glutathion reductase activity, and nitric oxide secretion were determined. It was found that 30 µmol/L CuCl2 might stimulate the exaltation and the compensatory proliferation of astrocytes. The survival rate of astrocytes in the 100 µmol/L CuCl2 group was significantly decreased relative to the 30 µmol/L CuCl2 group. At 24 hours of CuCl2 intervention, intracellular reduced glutathione level and glutathion reductase activity were significantly decreased in the 100 µmol/L CuCl2 group compared to the control group. At 120 hours of CuCl2 intervention, nitric oxide secretion in the 100 µmol/L CuCl2 group was significantly greater than in the control group. Under pathological conditions, excessive amounts of Cu(2+) greatly damaged the growth and proliferation of astrocytes, reduced the anti-oxidative capacity of astrocytes by reducing intracellular glutathione level and glutathion reductase activity, worsened oxidative stress, and activated inflammation pathway by increasing nitric oxide secretion. By the way, all these findings might provide potential molecular therapeutic targets for the neurodegenerative diseases related Cu(2+) Metabolic Disorders, e.g., Wilson's disease, Parkinson's disease and Alzheimer's disease.

Effect of heat shock pretreatment on apoptosis and metallothionein expression in rat cardiomyocytes.

To investigate the effect of heat shock pretreatment on apoptosis and mitochondrial metallothionein (MT) expression in rat cardiomyocytes. In vitro cultured H9C2 cells were randomly divided into three groups: control, hydrogen peroxide (H2O2) injury, and H2O2 injury after heat shock pretreatment (n = 6 per group). Cardiomyocyte apoptosis and caspase-3 activity were assayed after treatment. Mitochondrial cytochrome (cyt) c and MT expression was assayed by Western blotting. Compared with the control group, the H2O2 injury group had a growing number of apoptotic cardiomyocytes (P < 0.01) and significantly elevated caspase-3 activity (P < 0.01) with markedly increased mitochondrial cyt c and MT expression (P < 0.01). After heat shock pretreatment, the numbers of apoptotic and necrotic cardiomyocytes (P < 0.01) and the caspase-3 activity significantly declined (P < 0.01), while mitochondrial cyt c and MT expression continued to increase (P < 0.01) compared with the H2O2 injury group. Heat shock pretreatment inhibits cardiomyocyte apoptosis, which may have a protective effect on cardiomyocytes by increasing the expression of myocardial protective MT and reducing the release of mitochondrial cyt c.

Cerebral microemboli increase ß-amyloid protein deposition, MMP-9, and GFAP expression in the Alzheimer`s model of APP/PS1 double transgenic mice.

We investigated the effects of cerebral arterial microemboli on amyloid ß protein (Aß) deposition in the hippocampal region of amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice and evaluated the role of cerebral arterial microemboli in Alzheimer's disease (AD) pathogenesis. The mice were divided into a wild-type sham surgery group (n = 15), a wild-type coupled with microemboli group (n =15), an APP/PS1 double transgenic sham surgery group (n =15) and an APP/PS1 double transgenic coupled with microemboli group (n =15). The microemboli mice were injected via the left internal carotid artery with 300 µL of a normal saline suspension containing 100 whole blood clot-derived microemboli (25-50 µm). The sham surgery mice were injected with equal volumes of saline. After the mouse model was established for 1, 2 or 4 weeks, the Aß1-42 deposition in the left hippocampal region and the matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) expression levels were determined through immunohistochemical staining. The Aß1-42 deposition level in the left hippocampi of transgenic microemboli group was significantly greater than in the transgenic sham group at week 1 and 2 (P<0.001) but not at week 4. No Aß1-42 deposition was detected in the wild-type groups. Only sporadic MMP-9- and GFAP-positive cells were observed in the wild-type sham group. Significantly more MMP-9- and GFAP-positive cells were detected in the transgenic groups (P<0.001), particularly in the transgenic microemboli group. An intragroup analysis of the time factor for the microemboli groups showed significantly more MMP-9- and GFAP-positive cells at week 1 than at week 2 or 4 (P<0.001). No difference was detected between time points in the sham groups. Cerebral microemboli increased Aß deposition in the hippocampal region of APP/PS1 double transgenic mice. MMP-9 and GFAP expression may play an important role in excess Aß deposition, which is caused by an imbalance between the protein's synthesis and removal.

Downregulation of transketolase activity is related to inhibition of hippocampal progenitor cell proliferation induced by thiamine deficiency.

In animal experiments, hippocampal neurogenesis and the activity of thiamine-dependent transketolase decrease markedly under conditions of thiamine deficiency. To further investigate the effect of thiamine deficiency on the proliferation of hippocampal progenitor cells (HPCs) and the potential mechanisms involved in this effect, we cultured HPCs in vitro in the absence of thiamine and found that proliferation and transketolase activity were both significantly repressed. Furthermore, specific inhibition of transketolase activity by oxythiamine strongly inhibited HPC proliferation in a dose-dependent manner. However, thiamine deficiency itself inhibited the proliferation to a greater degree than did oxythiamine. Taken together, our results suggest that modulation of transketolase activity might be one of the mechanisms by which thiamine regulates the proliferation of hippocampal progenitor cells.

Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients.

OBJECTIVE: To observe the efficacy and toxicity of autologous hematopoietic stem cell transplantation (HSCT) in progressive multiple sclerosis (PMS). METHODOLOGY: Twenty-one patients with PMS were treated with autologous HSCT. Stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. After conditioning regimen of CY and total body irradiation or BEAM, stem cells were reinfused. CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion. The probabilities of confirmed progression-free survival and disease activity-free survival were used to assess the efficacy and the adverse experiences were recorded to detect the toxicities. RESULTS: The median follow-up time was 42 (6-65) months. The probabilities of confirmed progression-free survival and the disease activity-free survival were 75% and 33.3%, respectively. The principal adverse events included allergy, infection, elevation of liver enzymes, transient neurologic deterioration and depression. Two patients died of severe pneumonia and varicella-zoster virus hepatitis, at 4.5 and 15 months post-transplant, respectively. CONCLUSIONS: Autologous HSCT seems beneficial to PMS. However, more patients and longer follow up would be required to assess the risk/benefit ratio.