The effect of high egg intake on metabolic syndrome (MetS), a major risk factor for cardiovascular disease (CVD), has not been clearly elucidated. This study was conducted to review the literature related to egg consumption and the risk of metabolic disease as well as to examine the association between high egg intake and MetS in Korean adults. A literature review was conducted using published papers in PubMed and EMBASE through December 2017. We have reviewed 26 articles, which were associated with egg consumption and metabolic diseases, and found that the results were controversial. Therefore, we analyzed data from 23,993 Korean adults aged 19 yrs and older. MetS was defined based on criteria from the Adult Treatment Panel III. Egg consumption of 4-6 times/wk and 1 time/day were significantly associated with reduced prevalence of MetS (Odds ratio (OR)=0.82; 95% Confidence interval (CI)=0.71-0.95 for 4-6 times/wk, OR=0.83; 95% CI=0.69-0.99 for 1 time/day) compared to those who consumed eggs less than once monthly. However, consuming two or more eggs per day was not associated with MetS. As for the components of MetS, an egg intake of once daily decreased the prevalence of abdominal obesity and an intake of 2-7 eggs weekly was shown to prevent a reduction in the high-density lipoprotein cholesterol levels. This study suggests that while consuming eggs 4-7 times weekly is associated with a lower prevalence of MetS, consuming two or more eggs daily is not associated with a reduced risk for MetS.

Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

Cell density has profound impacts on the cell culture practices of human pluripotent stem cells. The regulation of cell growth, cell death, pluripotency and differentiation converge at high density, but it is largely unknown how different regulatory mechanisms act at this stage. We use a chemically defined medium to systemically examine cellular activities and the impact of medium components in high-density culture. We show that medium acidosis is the main factor that alters cell cycle, gene expression and cellular metabolism at high cell density. The low medium pH leads to inhibition of glucose consumption, cell cycle arrest, and subsequent cell death. At high cell density, the suppression of medium acidosis with sodium bicarbonate (NaHCO3) significantly increases culture capacity for stem cell survival, derivation, maintenance and differentiation. Our study provides a simple and effective tool to improve stem cell maintenance and applications.

We previously demonstrated that parathyroid hormone-related peptide (PTHrP) 1-84 knockin (Pthrp KI) mice, which lacked a PTHrP nuclear localization sequence (NLS) and C-terminus, displayed early senescence, defective osteoblastic bone formation, and skeletal growth retardation. However, the mechanism of action of the PTHrP NLS and C-terminus in regulating development of skeleton is still unclear. In this study, we examined alterations of oxidative stress and DNA damage response-related molecules in Pthrp KI skeletal tissue. We found that ROS levels, protein expression levels of γ-H2AX, a DNA damage marker, and the DNA damage response markers p-Chk2 and p53 were up-regulated, whereas gene expression levels of anti-oxidative enzymes were down-regulated significantly. We therefore further disrupted the DNA damage response pathway by deleting the Chk2 in Pthrp KI (Chk2-/-KI) mice and did comparison with WT, Chk2-/- and Pthrp KI littermates. The Pthrp KI mice with Chk2 deletion exhibited a longer lifespan, improvement in osteoblastic bone formation and skeletal growth including width of growth plates and length of long bones, trabecular and epiphyseal bone volume, BMD, osteoblast numbers, type I collagen and ALP positive bone areas, the numbers of total colony-forming unit fibroblasts (CFU-f), ALP+ CFU-f and the expression levels of osteogenic genes. In addition, the genes associated with anti-oxidative enzymes were up-regulated significantly, whereas the tumor suppressor genes related to senescence were down-regulated in Chk2-/- KI mice compared to Pthrp KI mice. Our results suggest that Chk2 deletion in Pthrp KI mice can somewhat rescue defects in osteoblastic bone formation and skeletal growth by enhancing endochondral bone formation and osteogenesis. These studies therefore indicate that the DNA damage checkpoint pathway may be a target for the nuclear action of PTHrP to regulate skeletal development and growth.

The biggest victim of ambient air pollution is the respiratory system. Mainly because of the harmful components, especially the particulate matters with an aerodynamic diameter of ≤ 2.5µm (PM2.5), can be directly inhaled and deeply penetrate into the lung alveoli, thus causing severe lung dysfunction, including chronic cough, bronchitis and asthma, even lung cancer. Unfortunately, the toxicological mechanisms of PM2.5 associations with these adverse respiratory outcomes have still not been clearly unveiled. Here, we found that PM2.5 rapidly induced inflammatory responses, oxidative injure and cell death in human bronchial epithelium cells through upregulation of IL-6 expression, ROS production and apoptosis. Furthermore, PM2.5 specifically induced nitric oxide synthase 2 (NOS2) expression and NO generation to elevate excessive autophagy. Finally, disruption of NOS2 signaling effectively blocked autophayosome formation and the subsequent cell death. Our novel findings systemically reveled the role of autophagy-mediated cell death in PM2.5-treated human bronchial epithelium cells and provided potential strategy for future clinic intervention.

Hepatocellular carcinoma (HCC) has become the second leading cause of cancer related death, with an increasing death rate in recent years. For advanced HCC, sorafenib is the first-line FDA approved drug, with no more than 3 months' overall survival advantage. Recently, a novel strategy has been proposed to improve sorafenib efficacy through enhancing the ability of sorafenib to induce cell death. STAT3 plays a key role in cancer development and recurrence by promoting cell proliferation, survival and immune evasion through its well-established function as a transcription factor in cancer. Notably, STAT3 transcription activity, indicated by its phosphorylation on Y705 is heterogeneous in different liver cancer cell lines. And sorafenib attenuates STAT3 phosphorylation on Y705. However, the role of STAT3 in sorafenib induced cell death is still largely unknown. Here, we show that liver cancer cells also exhibit heterogeneous sensitivities to sorafenib induced cell death, which co-relates with the STAT3-Y705 phosphorylation levels and JAK1/2 expression levels in Hep3B, Huh7 and HepG2 cells. Furthermore, overexpression or knockdown of STAT3 could switch HCC cells between resistant and sensitive to sorafenib induced cell death, which could be partially due to its regulation on Mcl-1, an anti-apoptotic protein. Finally, both inhibitors of STAT3 SH2 domain (S3i-201) or STAT3 upstream kinases JAKs (JAK inhibitor I) could synergistically enhance sorafenib induced cell death. Taken together, these data strongly suggest that STAT3 is not only a downstream effector of sorafenib, but also a key regulator of cellular sensitivity to sorafenib induced cell death, which provide support for the notion to develop STAT3-targeting drugs to improve clinical efficacy of sorafenib in liver cancer.

The mechanism of pain reduction involves bidirectional processes of pain blocking (nociception) and reductions in the levels of proinflammatory cytokines in the blood. Does transcutaneous electrical nerve stimulation (TENS) reduce blood levels of proinflammatory cytokines? For this systematic review, we searched in six databases to identify randomized controlled trials with the criteria: humans older than 18 years (adults), use of TENS in the experimental group, and having at least one pre- and postintervention blood level of at least one proinflammatory cytokine. The risk of bias and the level of evidence were assessed. Five studies were included involving 240 participants. The heterogeneity of the studies was high (I2: 85%); therefore, we used a random-effects meta-analysis. It was observed through the meta-analysis synthesis measures that there were statistically significant differences following the use of TENS to reduce the general group of cytokines. When grouped by chronic disease, by postoperative settings, or by individual studies in the case of IL-6, it was observed that the significant reduction of cytokines related to the use of TENS was maintained. The use of TENS reduced the blood levels of proinflammatory cytokines (we observed a protective factor of TENS in relation to inflammation). The protocol of the systematic review was registered in PROSPERO, CRD42017060379.

Measures of human physical capacity are required in ergonomic work design. To avoid biomechanical low-back overload, criteria are needed to differentiate load and overload. With respect to the evaluation of manual materials handling and similar physical exposures regarding potential overload, the compression component of the forces transferred via lumbar discs or vertebrae are compared with the ultimate compressive strength of lumbar-spine segments in a common biomechanical approach. As mechanical load-bearing capacity cannot be quantified directly in vivo, forces are applied to dissected spinal elements up to failure, which is interpreted as a measure of ultimate strength or tolerance to compression. Corresponding autopsy-material measurements were collected from literature and examined regarding several conditions: At the very minimum, a specimen consists of a complete vertebra or a disc including the adjacent endplates; failure is identified definitely as lumbar; compressive-force application is quasi-static; results are given as single values etc. This study continues previous collations, the latest is dated on 2001 including 25 usable out of 47 investigations totally. Currently, 66 newly discovered seemingly appropriate studies were collected via a systematic literature search, 11 of them were added for subsequent analysis. Nearly 4,000 values were compiled, 1,192 remained for analysis. Human lumbar ultimate compressive strength varies between 0.6 and 15.6 kN, mean and standard deviation are 4.84 ± 2.50 kN. For data originating from donors of specified gender and aged 20 years or more, the distributions are characterised by 6.09 ± 2.69 kN for male adults (n=305) and 3.95 ± 1.79 kN for female adults (n=205). According to a linear regression model for donors aged 20 years or more, strength significantly decreases with age: 10.43 kN minus 0.923 kN per 10 years of age for males and 7.65 kN minus 0.685 kN per decade for females. Based on these gendered age relations, the "Revised Dortmund Recommendations" were derived ranging between 5.4 kN for males aged 20 years and 2.2 kN for males of 60 years or more. The corresponding recommended limits for females amount to 4.1 and 1.8 kN, respectively. A specific safety margin was implemented for young adults up to 25 years of age as skeletal strength may not be fully developed. Due to the compression-related and biomechanical nature of this approach, other influences like shear or torsion as well as psychological or psychosocial risk factors remain unconsidered despite their undoubted importance for initiating complaints, disorders and diseases at the low-back region.

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.

Lipoprotein-A has been recognized as a risk factor for ischemic heart diseases. Myocardial infarction (MI) is common complication of ischemic heart disease. Diabetes play an incremental role in the development of coronary artery disease (CAD), however still there are conflicting data regarding the relationship of Lipoprotein-B and MI. We therefore wanted to evaluate the relationship of Lipo-B, MI and diabetes mellitus. Our objective was to determine the non-fasting Apo-lipoprotein B and triglycerides level among type II diabetic patients with ischemic heart disease and to compare with type II diabetic without ischemic heart disease.

To investigate the role of Intravitreal Bevacizumab (IVB), in preventing vitreo-retinal complications in patients of Eale's Disease (ED).

Previous studies have characterized the hepatoprotective and anti-inflammatory properties of oleanolic acid (OA). This study aimed to investigate the molecular mechanisms of OA hepatoprotection in concanavalin A- (ConA-) induced acute liver injury.

The expression of autophagy-related genes in cerebrospinal fluid of patients with tuberculous meningitis (TBM) and their clinical significance in patients with TBM was investigated. Sixty patients with TBM (observation group) and twenty healthy volunteers during the same period (control group) were selected and the cerebrospinal fluid was collected. The expression levels of p62, Beclin1 and LC3-II genes in cerebrospinal fluid were detected via semi-quantitative reverse transcription-polymerase chain reaction and patients in observation group were divided into high expression and normal or low expression group on the basis of LC3-II expression levels. On the other hand, the contents of inflammatory factors interleukin-6, -10 (IL-6, -10), and tumor necrosis factor-α (TNF-α) were detected using the enzyme-linked immunosorbent assay kit. The mRNA levels of p62, Beclin1 and LC3-II in cerebrospinal fluid of patients in observation were significantly higher than those in the control group (P<0.01). TUNEL assay showed that the apoptosis level of cerebro-spinal fluid in high expression was obviously lower than that in normal or low expression group (P<0.01); the content of IL-6 and TNF-α in cerebrospinal fluid in high expression was significantly lower than those in normal or low expression group (P<0.01); the content of IL-10 in cerebrospinal fluid in high expression was obviously higher than that in normal or low expression group (P<0.01). Correlation analysis revealed that LC3-II was positively correlated with IL-10, but negatively correlated with IL-6 and TNF-α. The mRNA levels of p62, Beclin1 and LC3-II in cerebrospinal fluid of patients with TBM are increased, there is a correlation between expression levels of autophagy-related genes and inflammatory factors, and the high expression of autophagy-related genes may have a protective effect on patients with TBM.

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low-dose mercury chloride (HgCl2). Agonist-induced contractions and relaxations were evaluated in isolated aortic rings from 3-month-old male Wistar rats treated by intra-muscular injection to caudal hind leg muscle with HgCl2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin- and luminol-enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low-dose HgCl2 administration impaired acetylcholine (ACh)-induced relaxation and potentiated phenylephrine- and serotonin-induced contractions in rat aortas. In addition, HgCl2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh-induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low-dose HgCl2 administration. EGT may serve as a therapeutic tool to reduce mercury-associated cardiovascular complications via improving the antioxidant status.

The correlation between coronary artery disease (CAD) and obstructive sleep apnea syndrome (OSAS) was investigated to analyze its risk factors. A total of 84 patients with suspected CAD due to chest tightness and pain or nocturnal angina, were selected. They were admitted and received coronary angiography in The Affiliated Hospital of Medical College Qingdao University from March, 2016 to June, 2017. The vital signs were monitored, and the sleep monitoring was performed before and after coronary angiography. Before angiography, the fasting blood was drawn for blood biochemical detection, followed by routine electrocardiogram and echocardiographic examination. In addition, the body mass index was calculated and whether patients suffered from hypertension and diabetes mellitus was observed. The patients were divided into the control group (patients with a negative coronary angiography) and the CAD group (patients with a positive coronary angiography). There were 34 cases in the control group, including 21 cases of OSAS (61.76%), and 50 in the CAD group, including 40 cases of OSAS (80.00%). Statistical analysis revealed that there were statistically significant differences in the apnea hypopnea index (AHI), lowest oxygen saturation, degree of coronary stenosis (Gensini score) and triglyceride level between the two groups (P<0.05). There were no statistically significant differences in the cholesterol level and prevalence rates of hypertension and diabetes mellitus between the two groups. Logistic regression analysis revealed that smoking and AHI >20 were the risk factors of CAD (OR=7.036 and 5.377). Thus, CAD is closely correlated with OSAS and AHI >20 is one of the risk factors of CAD.

The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have in vitro models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated. The results indicated that in the chemical model, the effect of hypoxia appeared in an early form at 6 h; whereas in the gas chamber the effect was slow and gradual and at 72 h there was an overexpression of erythropoietin (EPO), vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1α (HIF1α). In addition to the genes analyzed by reverse transcription-quantitative polymerase chain reaction, the global expression analysis between both models revealed the 9 most affected genes in common. The present study additionally identified 3 potential genes (lysyl oxidase, ankyrin repeat domain 37, B-cell lymphoma 2 interacting protein 3 like) previously identified in other studies, which may be considered as universal hypoxia genes along with HIF1α, EPO, VEGF, glucose transporter 1 (GLUT1), CA9, and LDH. To the best of the author's knowledge, this is the first time that both hypoxia models have been compared, and it was demonstrated that the effect of hypoxia induction was time sensitive in each model. These observations must be considered prior to selecting one of these models to identify selective hypoxia genes and their effects in cancer.

The effect of rosuvastatin on the expression of candidate gene polypeptide N-acetylgalactosaminyltrans ferase 3 (GALNT3) in atherosclerosis was studied. Sixty Wistar rats were randomly divided into the control (n=20), model (atherosclerosis group, n=20) and administration (rosuvastatin group, n=20) groups. The atherosclerosis model was established via injecting D3.6 million units of vitamin per kilogram of body weight and then the rats were fed with high-fat diet for 6 weeks. The total cholesterol, serum triglyceride and nitric oxide contents were detected using the kits, the morphological changes in thoracic aorta were observed via hematoxylin and eosin (H&E) staining, the mRNA expression of candidate gene GALNT3 was detected via reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of candidate gene GALNT3 was detected via western blot analysis. Compared with those in the control group, the contents of serum triglyceride and total cholesterol in the model group were significantly increased, and then significantly decreased after drug administration. Morphological observation showed that the surface of thoracic aorta was not smooth with endothelial shedding, and the smooth muscle cells were arranged irregularly and their number was obviously increased. Moreover, RT-PCR and western blot analysis revealed that the mRNA and protein expressions of GALNT3 were significantly increased in the administration group. Rosuvastatin can therefore significantly upregulate the expression of candidate gene GALNT3 in atherosclerosis, thereby reducing the incidence of atherosclerosis.

Eukaryotic translation initiation factor 3H subunit (EIF3H) is a member of the EIF3 family and exhibits a central role in translation initiation in higher eukaryotes. Although EIF3H expression is upregulated in numerous tumour types, its potential role in human osteosarcoma (OS) has not yet been investigated. In the present study, it was demonstrated that EIF3H mRNA expression was upregulated in the human OS cell lines Saos-2 and U2OS. A recombinant lentivirus harbouring short hairpin RNA targeting EIF3H was constructed and successfully infected human OS Saos-2 and U2OS cells, resulting in 95% downregulated EIF3H expression compared with the respective control groups. Knockdown of EIF3H significantly inhibited the proliferation and colony formation of OS cells in vitro, and tumour growth in nude mice in vivo. Flow cytometry analysis revealed cell cycle arrest and promotion of apoptosis in OS cells with EIF3H knocked down. In conclusion, the results strongly suggested that EIF3H is a critical factor mediating the growth of OS cells and may represent a novel therapeutic target.

The aim of the study was to identify key long non-coding RNAs (lncRNA) and related subpathways following severe burn injuries and research their functions. The miRNA-mRNA and lncRNA-miRNA interactions were downloaded from starBase v2.0 database. In addition, mRNA-miRNA interactions were obtained from TarBase, mirTarBase, mir2Disease, miRecords (V4.0) databases. The relationships of lncRNA-miRNA-mRNA were constructed. Genes of expression profiling were intersected with mRNA and lncRNA in lncRNA-mRNA interaction. Screened mRNAs were enriched into various pathways and screened lncRNAs were embedded into candidate pathways. Wallenius approximation methods were used to calculate the false discovery rate value of each sub-pathway. Based on the results of significant sub-pathways, the related lncRNA-mRNA network was constructed. A total of 18,081 genes were obtained. The lncRNA-mRNA intersections including 835 lncRNAs, 1,749 mRNAs and 7,693 interacting pairs were constructed. The enriched mRNAs were further enriched into various candidate pathways such as ribosome biogenesis in eukaryotes. Several sub-pathways were screened, including ribosome biogenesis in eukaryotes and MAPK signaling pathway. The network of pathway-lncRNA-mRNA was constructed. Hub-genes were identified, including C14orf169 and YLPM1. Several hub-lncRNAs were obtained, including PRKAG2 antisense RNA 1 and LEF1 antisense RNA 1. Several hub-lncRNAs including C14orf169, YLPM1, TTTY15, and PCBP1-AS1 were screened. The sub-pathways regulated by these lncRNAs were identified, and functions were predicted.

Retinoblastoma is the most common type of intraocular pediatric malignant tumor, which typically affects children <6 years of age. However, the underlying molecular mechanisms of retinoblastoma progression remain unclear. The aim of the present study was to investigate the function of long non-coding RNA (lncRNA) H19 in retinoblastoma clinical samples and cell lines, using reverse transcription-quantitative polymerase chain reaction, western blotting, colony formation, MTT, fluorescence activated cell sorting, cell invasion and migration, and in vivo growth assays. The results demonstrated that H19 may serve a critical oncogenic function in the progression of retinoblastoma, as lncRNA H19 levels were markedly increased in retinoblastoma cells and tissues compared with corresponding controls. In addition, patients with retinoblastoma with increased lncRNA H19 expression experienced poorer survival time compared with those with decreased lncRNA H19 levels. Knockdown of lncRNA H19 significantly suppressed retinoblastoma cell proliferation, migration and invasion in vitro and in vivo. Furthermore, lncRNA H19 expression was also associated with multiple proteins, including cyclin-dependent kinase 1, B-cell lymphoma-associated X protein, apoptosis regulator, tumor protein p53, vimentin, cadherin 13 and matrix metallopeptidase 9. In conclusion, lncRNA H19 may serve an important function in tumorigenesis and may be a potential target for therapy and prognosis in retinoblastoma.