• ISSN 16748301
  • CN 32-1810/R
Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes /issues, but are citable by Digital Object Identifier (DOI).
Increased expression of matrix metalloproteinase-1 (MMP-1) has been observed in the lesions of atherosclerosis and aneurysms; however, it is not fully understood whether macrophage-derived MMP-1 affects these diseases. To investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases, we generated transgenic (Tg) rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/promoter. Tg rabbits exhibited no visible abnormalities throughout their bodies. Western blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg rabbits. For the first experiment, Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks, and aortic and coronary atherosclerosis were evaluated. The gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits, but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic examination. For the second experiment, we generated aortic aneurysms by incubating with elastase. Compared with non-Tg rabbits, Tg rabbits exhibited a significantly greater aortic dilation. Increased macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and aneurysms. These results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.
Hepatic ischemic-reperfusion injury is a major cause of liver transplant failure, and is of increasing significance due to increased use of expanded criteria livers for transplantation. This review summarizes the mechanisms and protective strategies for hepatic ischemic-reperfusion injury in the context of liver transplantation. Pharmacological therapies, the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies. The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemic-reperfusion injury, and is an exciting and active area of research, which needs more study clinically.
Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.
Studies of the associations between maternal exposure to particulate matter (PM) and risk of adverse effects on fetal growth are inconsistent and inconclusive. Birth cohort studies are the best available study designed to answer this question, but so far the evidence from such studies has not been combined. We sought to assess the association between maternal exposure to PM and low birthweight (LBW) across 14 studies from 11 centers, and to explore the influence of trimester and exposure assessment methods on between-center heterogeneity in this association. Data were derived from PubMed, Embase, Google Scholar, CNKI, and WanFang database, references from relevant articles, and results from published studies until March 2017. A random-effects meta-analysis was used to combine the coefficient and odds ratios (OR) of individual studies conducted among 14 birth cohort studies. Results from random-effect meta-analysis suggested that a 17% and 6% increase in risk of LBW was associated with a 10 mg/m3 increase in PM2.5 and PM10 exposure concentrations at 3rd trimester (pooled odds ratios (OR), 1.17 and 1.06; 95% confidence interval (CI), 0.94–1.46 and 0.97-1.15, respectively), but our 95% CI included the null value. Our results showed a positive association between exposure to PM2.5 and PM10 during pregnancy and LBW based on birth cohort studies. However, neither reached formal statistical significance. This suggested that maternal exposure to PM may have adverse effects on birth outcomes. Additional mechanistic studies are necessary to confirm the relationship between PM pollution and LBW.
Fasudil, a selective rho kinase (ROCK) inhibitor, has been reported to play a beneficial role in systemic inflammation in acute lung injury, but its mechanism for ameliorating pulmonary edema and inflammation remains unclear. Using hematoxylin-and-eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay, quantitative real time PCR and Western blotting, we found that fasudil attenuated LPS-induced lung injury, decreased lung edema, and suppressed inflammatory responses including leukocyte infiltration and IL-6 production. Further, fasudil upregulated LPS-induced aquaporin 5 reduction and inhibited NF-kB activation in the lungs of mice. Our results suggest that fasudil could restore the expression of aquaporin 5 to eliminate LPS-induced lung edema and prevent LPS-induced pulmonary inflammation by blocking the inflammatory pathway. Collectively, blockade of the ROCK pathway by fasudil may be a potential strategy for the treatment of acute lung injury.
Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide (≤100 μmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.
Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of pro-inflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α. WDR5 enhances the ability of MKL1 to stimulate the promoter activities of pro-inflammatory genes. In contrast, silencing of WDR5 attenuates TNF-α induced production of pro-inflammatory mediators and erases the H3K4 methylation from the gene promoters. Of interest, the chromatin remodeling protein BRG1 also plays an essential role in maintaining H3K4 methylation on MKL1 target promoters by interacting with WDR5. MKL1 knockdown disrupts the interaction between BRG1 and WDR5. Together, our data illustrate a role for MKL1 in moderating the crosstalk between BRG1 and WDR5 to activate TNF-α induced pro-inflammatory transcription in macrophages.
Volatile anesthetic preconditioning has been shown to be a potent way to provide myocardium protection against ischemia/reperfusion (I/R) injury; however, this cardioprotection is lost in senescent animal models and elderly patients. NFkB-regulated genes have been linked to myocardial I/R injury and anesthetic preconditioning. Here, we investigated NFkB activation related to anesthetic preconditioning in aging rat myocardium. Isolated, Langendorff perfused rat hearts from Fischer 344 male rats, 24 months old, were randomly assigned to one of the three groups. The hearts of the control group were perfused with physiologic solution without any intervention. The hearts in the I/R group were subjected to 25 minutes ischemia and followed by 60 minutes reperfusion. The hearts in the treatment group were subjected to 10 minutes 2.5% sevoflurane, followed by 20 minutes washout and by 25 minutes ischemia and 60 minutes of reperfusion, respectively. Left ventricular developed pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP) were measured. Western blot analysis was used to measure inhibitor of kB (IkB) and anti-apoptotic genes: A1, ILP, c-IAP-2, Bcl-2, caspase 8 and caspase 9. Ischemia and reperfusion significantly decreased LVDP and increased LVEDP in aged rat hearts. Anesthetic preconditioning with sevoflurane did not change the effects I/R on LVDP and LVEDP, despite the fact that after treatment with anesthetic preconditioning, the levels of IκB, A1, ILP, caspase 8 and caspase 9 were significantly different compared to those of the control hearts. In conclusion, anesthetic preconditioning with sevoflurane does not improve myocardial systolic and diastolic functions. Our results suggest that the activation of NFkB regulated genes is different in the senescent myocardium and could account for loss of cardioprotection with aging.
The breakthrough discovery of cardiac natriuretic peptides provided the first direct demonstration of the connection between the heart and the kidneys for the maintenance of sodium and volume homeostasis in health and disease. Yet, little is still known about how the heart and other organs cross-talk. Here, we review three physiological mechanisms of communication linking the heart to other organs through: i) cardiac natriuretic peptides, ii) the microRNA-208a/ mediator complex subunit-13 axis and iii) the matrix metalloproteinase-2 (MMP-2)/C-C motif chemokine ligand-7/ cardiac secreted phospholipase A2 (sPLA2) axis – a pathway which likely applies to the many cytokines, which are cleaved and regulated by MMP-2. We also suggest experimental strategies to answer still open questions on the latter pathway. In short, we review evidence showing how the cardiac secretome influences the metabolic and inflammatory status of non-cardiac organs as well as the heart.
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to remove the major antigens [Gal, Neu5Gc, and Sd(a)] present on pig cells and tissues. Triple gene (GGTA1, CMAH, and β4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
Caspase-8 (CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism (-652 6N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk. To evaluate the association between the CASP8 -652 6N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model (del/del vs. ins/ins: OR = 0.82, 95%CI = 0.72–0.95; del/ins vs. ins/ins: OR = 0.92, 95%CI = 0.87–0.97; dominant model (del/ins + del/del vs. ins/ins: OR = 0.91, 95%CI = 0.87–0.96, recessive model: del/del vs. del/ins + ins/ins: OR = 0.85, 95%CI = 0.75–0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models, except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8 -652 6N del polymorphism and reduced digestive cancer risk, especially among Asians and population-based studies.
In this study, we sought to assess the safety and accuracy of sacropelvic fixation performed with image-guided sacroiliac screw placement using postoperative computed tomography and X-rays. The sacroiliac screws were placed with navigation in five patients. Intact specimens were mounted onto a six-degrees-of-freedom spine motion simulator. Long lumbosacral constructs using bilateral sacroiliac screws and bilateral S1 pedicle and iliac screws were tested in seven cadaveric spines. Nine sacroiliac screws were well-placed under an image guidance system (IGS); one was placed poorly without IGS with no symptoms. Both fixation techniques significantly reduced range of motion (P < 0.05) at L5–S1. The research concluded that rigid lumbosacral fixation can be achieved with sacroiliac screws, and image guidance improves its safety and accuracy. This new technique of image-guided sacroiliac screw insertion should prove useful in many types of fusion to the sacrum, particularly for patients with poor bone quality, complicated anatomy, infection, previous failed fusion and iliac harvesting.
Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n = 51; focal segmental glomerulosclerosis, n = 27; diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE ‘D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ‘I’ allele was assessed as having very weak association in cases of minimal change disease. ‘II’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of ‘ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.
Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node (RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para- and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter; therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.
Congestive heart failure (CHF) is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion. Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure. Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect. The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF, and concluded that long-term therapy with milrinone increased morbidity and mortality among patients with advanced CHF. Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways. Hence, we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes, thus leading to adverse clinical outcomes. We used rat cardiomyocyte cell line H9C2 and studied the impact of exposing cardiomyocytes to milrinone (10 mmol/L) for 24 hours on inflammatory gene expressions. RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay (41,000 genes). The following changes in inflammatory response-related gene expressions were discovered. Genes with increased expressions included:THBS2 (+ 9.98), MMP2 (+ 3.47), DDIT3 (+ 2.39), and ADORA3 (+ 3.5). Genes with decreased expressions were:SPP1 (- 5.28) and CD14 (- 2.05). We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes. However, further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.
As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study, the effect of Sonic Hedgehog (Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific antagonists. The effect of Shh signaling on MCF-7 cells was independent of Wnt5a, Dvl2 and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration via Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.
The prevalence of cardiovascular diseases (CVDs) is increasing at a rapid pace in developed countries, and CVDs are the leading cause of morbidity and mortality. Natural products and ethnomedicine have been shown to reduce the risk of CVDs. Schizonepeta (S.) tenuifolia is a medicinal plant widely used in China, Korea, and Japan and is known to exhibit anti-inflammatory, antioxidant, and immunomodulatory activities. We hypothesized that given herbal plant exhibit pharmacological activities against CVDs, we specifically explored its effects on platelet function. Platelet aggregation was evaluated using standard light transmission aggregometry. Intracellular calcium mobilization was assessed using Fura-2/AM, and granule secretion (ATP release) was measured in a luminometer. Fibrinogen binding to integrin αⅡbβ3, was assessed using flow cytometry. Phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules and activation of the protein kinase B (Akt) was assessed using Western blot assays. S. tenuifolia, extract potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αⅡbβ3. Moreover, all extracts significantly inhibited MAPK and Akt phosphorylation. S. tenuifolia extract inhibited platelet aggregation and granule secretion, and attenuated collagen mediated GPVI downstream signaling, indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function. We suggest that S. tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.
It has been shown that stem cells are able to calcify both in vitro and in vivo once implanted under the skin, if conveniently differentiated. Nowadays, however, a study on their efficiency in osseous regeneration does not exist in scientific literature and this very task is the real aim of the present experimentation. Five different defects of 6 mm in diameter and 2 mm in depth were created in the calvaria of 8 white New Zealand rabbits. Four defects were regenerated using 2 different conveniently modified scaffolds (Bio-Oss® Block and Bio-Oss Collagen®, Geistlich), with and without the aid of stem cells. After the insertion, the part was covered with a collagen membrane fixed by 5 modified titan pins (Altapin®). The defect in the front was left empty on purpose as an internal control to each animal. Two animals were sacrificed respectively after 2, 4, 6, 10 weeks. The samples were evaluated with micro-CT and histological analysis. Micro-CT analysis revealed that the quantity of new bone for samples with Bio-Oss® Block and stem cells was higher than for samples with Bio-Oss® Block alone. Histological analysis showed that regeneration occurred in an optimal way in every sample treated with scaffolds. The findings indicated that the use of adult stem cells combined with scaffolds accelerated some steps in normal osseous regeneration.
Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This study aimed to assess possible association between rs4938723 polymorphism and bladder cancer risk. This case-control study was done on 136 pathologically proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c rs4938723 polymorphism was achieved by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Our findings did not show any statistically significant differences in genotype and allele frequencies between bladder cancer and controls. Larger sample sizes with diverse ethnicities are required to validate our findings.
Renal dysfunction is a common side-effect of chemotherapeutic agents in patients with hematopathy. Although broadly used, glomerular filtration rate (GFR) estimation equations were not fully validated in this specific population. Thus, this study was designed to further assess the accuracy of various GFR equations, including the newly 2012 CKD-EPI equations. Referring to 99mTc-DTPA clearance method, three Scr-based (MDRD, Peking, and CKD-EPIScr), three Scys C-based (Steven 1, Steven 2, and CKD-EPIScys C), and three Scr-Scys C combination based (Ma, Steven 3, and CKD-EPIScr-Scys C) equations were included. Bias, P30, and misclassification rate were applied to compare the applicability of the selected equations. A total of 180 Chinese hematological patients were enrolled. Mean bias, absolute mean bias, P30, misclassification rate and Bland-Altman plots of the CKD-EPIScr-Scys C equation were 7.90 mL/minute/1.73 m2, 17.77 mL/minute/1.73 m2, 73.3%, 38% and 79.7 mL/minute/1.73 m2, respectively. CKD-EPIScr-Scys C predicted the most precise eGFR both in lymphoma and leukemia subgroups. Additionally, CKD-EPIScys C equation in the rGFR ≧ 90 mL/minute/1.73 m2 subgroup and Steven 2 equation in the rGFR < 90 mL/ minute/1.73 m2 subgroup provided more accurate estimates in each subgroup. The CKD-EPIScr-Scys C equation could be recommended to monitor kidney function in hematopathy patients. The accuracy of GFR equations may be closely related with GFR level and kidney function markers, but not the primary cause of hematopathy.
To evaluate the effect of methotrexate on collagen-induced arthritis, micro-computed tomography (micro-CT) and histopathological analyses were used in male Wistar rats. Rats were divided randomly into three groups. Group 1 was treated with 0.9% saline, and groups 2 and 3 were boosted with type Ⅱ collagen. From day 21 to 42, groups 1 and 2 were orally treated with 0.9% saline and group 3 was orally treated with 1.5 mg/kg methotrexate. All rats were sacrificed at day 42 after the first collagen treatment. Micro-CT analyses showed bony parameters, such as bone volume and trabecular number, were decreased in group 2 compared to group 1, and these parameters were recovered in group 3. Histopathological examination and pathological parameter scoring showed that the knee joints of rats in group 2 had severe joint destruction, showing cartilage and bone erosion, enlarged cavities with inflammatory cell infiltration and activation of synovial fibroblasts. By contrast, these changes were reduced in group 3. Taken together, methotrexate treatment showed therapeutic potential in male rat collagen-induced arthritis model, and micro-CT analysis and histopathological tools could be integrated to assess the quantification/qualification of arthritic lesions.
Contrary to freezing preservation and formalin embalming, Thiel embalmed cadaver presents soft texture and color very close to that of living organism, and many applications based on Thiel embalmed cadavers have been reported. However, Thiel embalmed cadavers cannot be used as reliable evaluation model for radiofrequency ablation (RFA) due to dramatic changes of electrical conductivity in the embalmed tissue. To address this issue, we investigated various modifications of the original Thiel embalming solution. By altering the chemicals' species and concentration we figured out a formula that can greatly reduce the embalming fluid's electrical conductivity without significantly compromising the 18-day embalmed kidney samples' suppleness and color. We also investigated a two-stage embalming technique by first submerging the kidney sample into original Thiel's tank fluid for 28 days, then the sample was withdrawn from the tank fluid and placed into modified dilution fluids for additional two weeks. Stiffening and discoloration occurred in these diluted samples implying the reversibility of Thiel-embalmed tissues' suppleness and color with the removal of the strong electrolytes. This study presents a modified embalming method which could be used for RFA evaluation and also helps our understanding of the mechanism of embalmment process.
Multivessel coronary artery ectasia with severe calcification is rare among patients with coronary artery disease. A 74-year-old Chinese woman suffered from acute myocardial infarction on a background of 50 years of poorly controlled hypertension secondary to pheochromocytoma, which was surgically removed in June 2012 prior to the presentation. Coronary angiography revealed total occlusion of the proximal left anterior descending artery, and multiple ectasias with severe calcification in the left main, circumflex and right coronary artery. After an aspiration thrombectomy and balloon angioplasty, grade 3 coronary flow was restored in the left descending coronary artery. No cardiac events were found in the 12-month follow-up. We conclude that multivessel coronary artery ectasia and severe calcification may be present in patients with a long-standing history of hypertension secondary to pheochromocytoma.
Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6, ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients. CCRL2, a presumed member of the atypical chemokine receptor family, plays a key role in lung dendritic cell trafficking to peripheral lymph nodes. Recent studies have reported the expression of CCRL2 in different human cancer cell lines and tissues. However, its function and expression in prostate cancer has not been previously addressed.
The Journal of Biomedical Research--2019, 33(2)
REVIEW ARTICLE
Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function (LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia (FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.
ORIGINAL ARTICLE
The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the Pglycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.
Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds:hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease (AD). We analyzed by an inverse docking procedure (INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE, PSEN, IDE, CASP, calpain and TNF-α, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.
The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.
Despite their potential applications in future regenerative medicine, periodontal ligament stem cells (PDLSCs) are difficult to obtain in large amounts from patients. Therefore, maintaining stemness while expanding the cell numbers for medical use is the key to transitioning PDLSCs from the bench to the clinic. Lysophosphatidic acid (LPA), which is present in the human body and saliva, is a signaling molecule derived from phospholipids. In this study, we examined the effects of LPA on stemness maintenance in human PDLSCs. Several spindle-shaped and fibroblast-like periodontal ligament stem-like cell lines were established from PDLSC isolation. Among these cell lines, the most morphologically appropriate cell line was characterized. The expression levels of OCT4, NANOG (a stem cell marker), and CD90 (a mesenchymal stem cell marker) were high. However, CD73 (a negative marker of mesenchymal stem cells) expression was not observed. Notably, immunofluorescence analysis identified the expression of STRO-1, CD146 (a mesenchymal stem cell marker), and sex determining region Y-box 2 at the protein level. In addition, lipid droplets were stained by Oil red O after the induction of adipogenesis for 21 days, and mineralized nodules were stained by Alizarin Red S after the induction of osteogenesis for 14 days. Alkaline phosphate staining also demonstrated the occurrence of osteogenesis. In summary, we established a human PDLSC line, which could be applied as a cell source for tissue regeneration in dental patients. However, further studies are needed to determine the detailed effects of LPA on PDLSCs.
This study was designed to compare the impact of post and core systems on resistance to fracture of endodontically treated anterior teeth with flared root canals and to assess their fracture pattern. Sixty central incisors were cut horizontally 2 mm coronal to the cementoenamel junction (CEJ). After root canal therapy, teeth were assigned into 6 groups (n=10 each) based on a post system and used as follows:Group C, non-flared root received size #1 glass fiber posts (Control); Group AP, flared root restored with anatomical post; Group RC, flared root restored with size #1 fiber post and cemented with thick layer of resin cement; Group CR, flared root restored with size #1 and reinforced with composite resin; Group CM, cast post-core; Group CP, CAD/CAM polymer-infiltrated ceramic post and core. Following post cementation, core build-up and crown insertion, the specimens were thermo-cycled up to 10, 000 cycles (5C/55C; 30 seconds dwell time, 6 seconds transition time) and then statically loaded at 1 mm/minute crosshead speed using a universal testing machine. One-way ANOVA and Tukey HSD post hoc test (α=0.05) were used for data analysis. Group C recorded significantly higher resistance to fracture values[(826.9±39.1) N] followed by group CP[(793.8±55.6) N] while group RC yielded the lowest fracture resistance values[(586.7±51.4) N]. The resistance to fracture of wide root canals can be enhanced by using one-piece CAM/CAM post and core as an alternative to the use of either glass fiber post, relined with composite resin increasing the thickness of luting cement or the use of cast post and core system. However, this was an in vitro investigation and further in vivo studies are necessary.
This study was conducted to investigate the maxillary denture bases and occlusal discrepancies using the Vertex Thermosens in comparison with the conventional polymethyl-methacrylate materials. Twenty maxillary denture bases were prepared from the Vertex ThermoSens and a conventional heat-cured denture base materials. Acrylic maxillary second molars were arranged in their respective positions on the ridge. After curing of both types of denture bases, they were deflasked with their respective master casts. Reference points were prepared for measurements of the antero-posterior and cross-arch dimensions at the denture borders using caliper device. Furthermore, the teeth discrepancies were measured between reference points in the ligual aspect of the second maxillary molars. The recorded data was analyzed using SPSS statistical software version 20. The results showed initial shrinkage of both denture bases in the antero-posterior and cross-arch dimensions immediately after decasting. This contraction was compensated gradually during storage in water up to 2 weeks. Regarding the variable time, there was a significant difference between the tested materials. Moreover, the results revealed occlusal discrepancies and shifting of teeth inward immediately after decasting, followed by outward movement after storage in water for 2 weeks. Regarding the variables time and materials, there were significant differences. Both materials exhibited inward shrinkage in the antero-posterior and cross-arch dimensions immediately after decasting. Both denture bases showed inward shifting of teeth immediately after decasting, followed by outward movement after storage in water up to 2 weeks.
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage
Hanpeng Huang, Xiaoyu Li, Yan Zhuang, Nan Li, Xudong Zhu, Jin Hu, Jingjing Ben, Qing Yang, Hui Bai, Qi Chen
2014, 28(3): 213-221.   doi: 10.7555/JBR.28.20130105
+Abstract [PDF 11938KB](0)
Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats
Ravi Prakash Rao, Ansima Singh, Arun K Jain, Bhartu Parsharthi Srinivasan
2011, 25(6): 411-417.   doi: 10.1016/S1674-8301(11)60054-7
+Abstract [PDF 1946KB](0)
A clinical perspective on mucoadhesive buccal drug delivery systems
Ritu MGilhotra, Mohd Ikram, Sunny Srivastava, Neeraj Gilhotra
2014, 28(2): 81-97.   doi: 10.7555/JBR.27.20120136
+Abstract [PDF 2322KB](0)
AEG-1 expression correlates with CD133 and PPP6c levels in human glioma tissues
Jia Guo, Xin Chen, Ruxing Xi, Yuwei Chang, Xuanwei Zhang, Xiaozhi Zhang
2014, 28(5): 388-395.   doi: 10.7555/JBR.28.20140015
+Abstract [PDF 14254KB](0)
Lipoprotein metabolism in nonalcoholic fatty liver disease
Zhenghui Gordon Jiang, Simon C. Robson, Zemin Yao
2013, 27(1): 1-13.   doi: 10.7555/JBR.27.20120077
+Abstract [PDF 1247KB](0)
ApoB/apoA1 is an effective predictor of coronary heart disease risk in overweight and obesity
Min Lu, Qun Lu, Yong Zhang, Gang Tian
2011, 25(4): 266-273.   doi: 10.1016/S1674-8301(11)60036-5
+Abstract [PDF 1143KB](0)
Development of Leishmania vaccines: predicting the future from past and present experience
Joshua Muli Mutiso, John Chege Macharia, Maria Ndunge Kiio, James Maina Ichagichu, Hitler Rikoi, Michael Muita Gicheru
2013, 27(2): 85-102.   doi: 10.7555/JBR.27.20120064
+Abstract [PDF 1050KB](0)
Atrial fibrillation
Thomas M. Munger, Li-Qun Wu, Win K. Shen
2014, 28(1): 1-17.   doi: 10.7555/JBR.28.20130191
+Abstract [PDF 5351KB](0)
Maternal risk factors for low birth weight for term births in a developed region in China: a hospital-based study of 55,633 pregnancies
Yihua Bian, Zhan Zhang, Qiao Liu, Di Wu, Shoulin Wang
2013, 27(1): 14-22.   doi: 10.7555/JBR.27.20120046
+Abstract [PDF 1263KB](0)
Fracture resistance of posterior teeth restored with modern restorative materials
Ibrahim M. Hamouda, Salah H. Shehata
2011, 25(6): 418-424.   doi: 10.1016/S1674-8301(11)60055-9
+Abstract [PDF 762KB](0)