Abstract:Innate immunity is considered to provide the initial defense against infections by viruses, bacteria, fungi, and protozoa. Detection of the signature molecules of invading pathogens by front-line defense cells via various germline-encoded pattern recognition receptors (PRRs) is needed to activate intracellular signaling cascades that lead to transcriptional expression of inflammatory mediators to coordinate the elimination of pathogens and infected cells. To maintain a fine balance between protective immunity and inflammatory pathology upon infection, the innate signaling pathways in the host need to be tightly regulated. MicroRNAs (miRNAs), a new class of small non-coding RNAs, have been recently shown to be potent modulators that function at post-transcriptional levels. Accumulating evidence demonstrates that the involvement of microorganism-encoded and host miRNAs might play instructive roles in the immune response upon infection. Here, we discuss the current knowledge of miRNAs in the regulation of immune response against infections.
Abstract:Epstein-Barr virus (EBV), a human gammaherpesvirus carried by more than 90% of the world’s population, is associated with malignant tumors such as Burkitt’s lymphoma (BL), Hodgkin lymphoma, post-transplant lymphoma, extra-nodal natural killer/T cell lymphoma, and nasopharyngeal and gastric carcinomas in immune-compromised patients. In the process of infection, EBV faces challenges: the host cell environment is harsh, and the survival and apoptosis of host cells are precisely regulated. Only when host cells receive sufficient survival signals may they immortalize. To establish efficiently a lytic or long-term latent infection, EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways. This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors, which decide the fate of the host cell. The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma (Bcl) family are unknown. Still, EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host. We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.
Keywords:Epstein-Barr virus;Bcl family members;Apoptosis;Drugs therapy
Abstract:Objective:To investigate the relationship between growth patterns and mandibular posterior tooth-alveolar bone complex morphology in a Chinese population with normal occlusion.Methods:Forty-five patients with normal occlusion (23 males, 22 females) were included in this study. Among these patients, 20 displayed the vertical growth pattern, and 20 had the horizontal growth pattern, while the remaining patients displayed the average growth pattern. All of the patients underwent dental cone beam computed tomography (CBCT), which included the region of the mandibular posterior teeth and the alveolar. A linear regression analysis and a correlation analysis between the facial height index (FHI) and the alveolar bone morphology were performed.Results:The inclination of the molars, the thickness of the cortical bone, and the height of the mandibular bone differed significantly between patients with the horizontal growth pattern and those with the vertical growth pattern (P<0.05). Significant positive correlations were found between: the FHI and the inclination of the molars; the FHI and the thickness of the cortical bone; and the FHI and the height of the mandibular bone.Conclusions:The mandibular posterior tooth-alveolar bone complex morphology may be affected by growth patterns.
Abstract:A total of 50 does were used to determine selected hematological and biochemical parameters with special references to oxidative stress markers, acute phase protein profiles, and proinflammatory cytokines in healthy and gangrenous mastitis affected does. Animals were divided into two equal groups represented as clinically healthy (control) and diseased groups, respectively. The bacteriological examination of milk samples from diseased does revealed many types of bacterial infection. The isolated bacteria were Staphylococcus aureus (N=23/25), Escherichia coli (N=11/25), and Clostridium perfringens (N=4/25). There was a significant increase in the levels of β-hydroxybutyrate, non-esterified free fatty acids, triglyceride, low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase, and alanine aminotransferase and a significant reduction in the levels of glucose, cholesterol, and high density lipoprotein cholesterol (HDL-C) in does with gangrenous mastitis compared to healthy does. Moreover, there was a significant increase in the levels of malondialdehyde and uric acid with a significant decrease in the levels of reduced glutathione, super oxide dismutase, and catalase in does with gangrenous mastitis compared to healthy does. In addition, there was a significant increase in the haptoglobin, serum amyloid A, fibrinogen, interleukin 6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in does with gangrenous mastitis compared to healthy ones. Conclusively, oxidative stress biomarkers, acute phase proteins, and proinflammatory cytokines play an essential task as biomarkers for gangrenous mastitis in does. Mastitis may be considered as one of the ketotic stressors in does after parturition.
Abstract:Peroxynitrite (ONOO−) is a powerful oxidant and nitrosative agent and has in vivo existence. The half life of ONOO− at physiological pH is less than 1 s. It can react with nucleic acids, proteins, lipoproteins, saccharides, cardiolipin, etc., and can modify their native structures. Action of ONOO−, synthesized in the authors’ laboratory by a rapid quenched flow process, on structural changes of commercially available RNA was studied by ultraviolet (UV), fluorescence, and agarose gel electrophoresis. Compared to native RNA, the ONOO−-modified RNA showed hyperchromicity at 260 nm. Furthermore, the ethidium bromide (EtBr) assisted emission intensities of ONOO−-modified RNA samples were found to be lower than the emission intensity of native RNA-EtBr complex. Agarose gel electrophoresis of ONOO−-modified RNA showed a gradual decrease in band intensities compared to native RNA, an observation clearly due to the poor intercalation of EtBr with ONOO−-modified RNA. Native and ONOO−-modified RNA samples were used as an antigen to detect autoantibodies in sera of patients with clinically defined breast cancer. Both direct binding and inhibition enzyme-linked immunosorbent assay (ELISA) confirmed the prevalence of native and 0.8 mmol/L ONOO−-modified RNA specific autoantibodies in breast cancer patients. Moreover, the progressive retardation in the mobility of immune complexes formed with native or 0.8 mmol/L ONOO−-modified RNA and affinity purified immunoglobulin G (IgG) from sera of breast cancer patients supports the findings of the direct binding and inhibition ELISAs. The peroxynitrite treatment to RNA at a higher concentration appears to have damaged or destroyed the typical epitopes on RNA and thus there was a sharp decrease in autoantibodies binding to 1.4 mmol/L ONOO−-modified RNA. It may be interpreted that cellular nitrosative stress can modify and confer immunogenicity on RNA molecules. Higher concentrations of nitrogen reactive species can be detrimental to RNA. However, the emergence of native as well as 0.8 mmol/L ONOO−-modified RNA as a novel antigen/substrate for autoantibodies in breast cancer patients indicates that, in future, these molecules might find a place on the panel of antigens for early diagnosis of breast cancer.
Abstract:The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)AA+AG: 0.654, 95% confidence interval (CI): 0.406–1.055; P=0.082), rs4233532 (ORCC: 1.667, 95% CI: 0.967–2.876; ORCT: 1.435, 95% CI: 0.998–2.063; P=0.077), and rs2881930 (ORCC: 0.263, 95% CI: 0.095–0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (ORAA+AG: 1.233, 95% CI: 0.903–1.683), rs4233532 (ORCC: 0.892, 95% CI: 0.640–1.243; ORCT: 1.134, 95% CI: 0.897–1.433), and rs2881930 (ORCC: 1.096, 95% CI: 0.620–1.938; ORCT: 1.009, 95% CI: 0.801–1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319–2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.
Keywords:CASP9;CASP10;Colorectal cancer;Single nucleotide polymorphisms;Susceptibility to cancer;Tea drinking
Abstract:The soft-shelled turtle Pelodiscus sinensis is a high-profile turtle species because of its nutritional and medicinal value in Asian countries. However, little is known about the genes that are involved in formation of their nutritional quality traits, especially the molecular mechanisms responsible for unsaturated fatty acid and collagen biosynthesis. In the present study, the transcriptomes from six tissues from Pelodiscus sinensis were sequenced using an Illumina paired-end sequencing platform. We obtained more than 47 million sequencing reads and 73 954 unigenes with an average size of 754 bp by de-novo assembly. In total, 55.19% of the unigenes (40 814) had significant similarity with proteins in the National Center of Biotechnology Information (NCBI) non-redundant protein database and Swiss-Prot database (E-value <10−5). Of these annotated unigenes, 9 156 and 11 947 unigenes were assigned to 52 gene ontology categories (GO) and 25 clusters of orthologous groups (COG), respectively. In total, 26 496 (35.83%) unigenes were assigned to 242 pathways using the Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG). In addition, we found a number of highly expressed genes involved in the regulation of P. sinensis unsaturated fatty acid biosynthesis and collagen formation, including desaturases, growth factors, transcription factors, and extracellular matrix components. Our data represent the most comprehensive sequence resource available for the Chinese soft-shelled turtle and could provide a basis for new research on this turtle as well as the molecular genetics and functional genomics of other terrapins. To our knowledge, we report for the first time, the large-scale RNA sequencing (RNA-Seq) of terrapin animals and would enrich the knowledge of turtles for future research.
Abstract:Background and objective:Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum (Compositae), a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 (MMP-9) in the onset of HSOS induced by Gynura segetum.Methods:Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy (TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) methods. Results:A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations (alanine aminotransferase (ALT): (84.8±13.62) vs. (167.0±72.63) U/L, P<0.05; aspartate aminotransferase (AST): (27.6±6.31) vs. (232.8±108.58) U/L, P<0.05). Hematoxylin and eosin (H&E) staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hemorrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased. Conclusions:MMP-9 may have an important role in early pathological changes of HSOS, and thus the onset of the disease.
Abstract:The diagnosis of extra-pulmonary tuberculosis (TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis. We report four cases of extra-pulmonary tuberculosis on dialysis, with two cases on peritoneal dialysis and two cases on hemodialysis. The presentations, therapy, and outcomes of TB infection in these patients were reviewed. Otherwise, the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed. A total of 61 studies containing 70 cases were included. The most common primary disease was diabetic nephropathy (22.86%, 16/70). The peritoneum (31.42%, 22/70), bone (21.42%, 15/70), and lymph node (20%, 14/70) were the most frequently infected. Single organ infection was common (90%, 63/70). Fever (58.57%, 41/70), pain (35.71%, 25/70), and enlarged lymph node (20%, 14/70) were the most common symptoms. Biopsy (67.14%, 47/70) and culture (40%, 28/70) provided most reliable methods for clear diagnosis of tuberculosis. The combined treatment of isoniazid, rifampicin, pyrazinamide, and ethambutol (44.29%, 31/70) was the most common therapy. The majority of patients improved (82.86%, 58/70); however, 12 cases got worse (17.14%), with 10 of them dying (14.29%). Physicians should be aware of the non-specific symptoms and location of infection, and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever, pain, and weight loss.