ISSN 1673-6184 CN 31-1966/R
Epstein-Barr virus (EBV) is the first virus found in humans to be associated with tumorigenesis. More and more studies have found that EBV infection is closely related with the occurrence, development, treatment and prognosis of some lymphomas. To date, although the application of antiviral drugs and immunotherapy is rapidly developed, the treatment against EBV-positive lymphomas is still mainly based on radiotherapy and chemotherapy. To strengthen the research on EBV and EBV-related lymphomas, and seeking effective prevention or treatment strategies against EBV infection, will be expected to improve the prognosis of patients with EBV-positive lymphomas.
Whooping cough is a highly contagious and acute respiratory disease which mainly affects children. Bordetella pertussis is responsible for a majority of these cases. Despite widespread vaccination, re-emergence of pertussis has been reported both in developed and developing countries. It is necessary to develop new vaccine candidates with high effectiveness. In this study, we constructed a live attenuated strain named BPTM1, in which two genes encoding major toxins PTX and DNT were removed, and a third gene, ampG, responsible for the transportation of toxin TCT was replaced by a homologous gene from Escherichia coli, by homologous recombination. The decreased expression of S1 of PTX was supported by Western bolting. The knock-out or replacement of three genes was confirmed at DNA level by polymerase chain reaction (PCR). The attenuated strain, BPTM1, showed growth curves in vitro and colonization curves in vivo similar to the parent strain BPMM. Although BPTM1 had a significant reduction in lung pathology than BMMM, it induced the same levels of antibodies IgG, IgG1, IgG2a as BPMM. These results suggest that attenuated Bordetella pertussis BPTM1 may become a candidate vaccine for pertussis vaccine.
Ureaplasma urealyticum (U. urealyticum) is a very important pathogenic microorganism. In view of a worsen resistance of U. urealyticum to antibiotics recently, it’s in great need to exploit new alternative therapies for U. urealyticum infections. The aim of this research is to study the in vitro susceptibility of U. urealyticum to toluidine blue-mediated photodynamic antimicrobial chemotherapy (PACT). Two biovars of U. urealyticum including two standard strains and two clinical strains were incubated with photosensitizer toluidine blue with different concentrations from 2.5 to 0.039 062 5 mmol/L. After 20 or 60 min incubation, they were treated with (633±10) nm red light source, with four different light fluences including 48, 102, 204 and 408 mJ/cm2. The association between the incubation time, toluidine blue concentration, as well as the light fluence and PACT effect on U. urealyticum was evaluated 48 h after treatment. Besides, the difference in response to PACT between the two biovars of U. urealyticum was also analyzed. The results showed that PACT had an inactivation effect on the growth of U. urealyticum, in a toluidine blue concentration-dependent and fluence-dependent manner. Longer incubation time induced more extensive inactivation of U. urealyticum. No significant difference in susceptibility to PACT was observed between the two biovars of U. urealyticum. It is concluded that toluidine blue-mediated PACT can inactivate U. urealyticum in vitro, and this therapy may become a promising alternative treatment for U. urealyticum infections.
The compound HY-152E with anti-tuberculosis activity is a small molecule with good anti-tuberculosis activity (MIC≤0.09 μg/mL) in our previously observations (Patent No. ZL201210088290.0). In order to identify the anti-tuberculosis action model of compound HY-152E, the potential direct-binding target of Mycobacterium tuberculosis, which may interact with the compound HY-152E, is analyzed by drug affinity responsive target stability (DARTS) technique and mass spectrometry. DARTS is a general methodology for identifying and studying protein-ligand interactions. The technique is based on the principle that when a small molecule compound binds to a protein, the interaction stabilizes the target protein’s structure such that it becomes protease resistant. Compound HY-152E was added into protein lysates of Mycobacterium tuberculosis H37Ra, and then the samples with or without compound HY-152E were digested using streptomycin protease with different concentrations for 30, 40 or 60 min. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results showed that there were two differential bands at 70 000 and 45 000-55 000, respectively in different proteolysis samples. The protein information of the two different bands was analyzed using mass spectrometry, and 86 proteins were identified. Nine potential protein targets of compound HY-152E against tuberculosis were screened out after information searching and functional analysis with tuberculosis database. The determination of these potential targets lays the foundation for the further research of anti-tuberculosis molecular mechanism of compound HY-152E.
In recent years, a series of new viruses were isolated through co-culture with amoebae. These viruses, generally named as “giant viruses” with large virus particles as well as huge genomes, were found to be widely spread over the world. The fact that they encode genes involved in protein synthesis triggered discussion on the issues such as the viral nature and origin. Giant viruses also have the potential to be pathogenic to humans. Here, we reviewed the recent progress on serological, molecular biological, metagenomic detection, and virus isolation of two giant viruses, Mimivirus and Marseillevirus, in human samples, as well as their infection and pathogenesis in mammalian cell lines and animal models.
Human papillomavirus (HPV) is the causative pathogen of over 98% of cervical cancer, which is the second most common cancer in women worldwide. Prior to the development of cancer, HPV establishes persistent infections in the genital tract and successfully evades immune clearance. Members of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) family are important regulators of the innate immune response. HPV proteins can downregulate the expression of STAT1 to allow for stable maintenance of viral episome. STAT5 is another member of this pathway, which plays an important role in controlling cell cycle progression. Several studies reveal that STAT5 is activated in HPV-positive cells and it is necessary for HPV genome amplification. Persistent infection of HPV interacts with abnormal expression of STAT proteins and contributes to the development of cervical cancer. Targeting of these pathways by pharmaceuticals can inhibit HPV infection, which will contribute to the treatment of cervical cancer. The article summarizes the progress on the relationship between HPV and STAT pathway.
Interferons (IFNs) are key cytokines with multifaceted antiviral and immunoregulatory properties. Three distinct types of IFN are recognized (I–III) based on structural features, receptor, cellular source and biological activities. The action of IFNs is mediated by a complex, partially overlapping, transcriptional program initiated by the interaction with specific receptors. Genetic diversity, with polymorphisms and mutations, can modulate the extent of IFN responses and the susceptibility to infections. Almost all viruses developed mechanisms to subvert the IFN response, involving both IFN induction and downstream effector mechanisms. Interactions between IFN types may occur, for both antiviral and immunoregulatory effects, in a complex interplay, involving both synergistic and antagonistic effects. In this paper, the aspects of IFN genetic diversity, viral strategies to counteract the IFN and synergistic and antagonistic interactions between IFN types are reviewed, in order to better understand the antiviral effect of interferon.
Bacterial brain abscess refers to a focal, intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus caused by bacteria. Though the attack rate is rather low, it may lead to severe consequences, even lethal. In terms of etiology, there is a correlation between predisposing factors in patients and pathogens that cause the infection, among which, Streptococcus and Staphylococcus are the most common. In China, so as in Asia, Gram-negative bacilli also make a large part. In clinical practice, the combination of the third generation of cephalosporins and metronidazole, which covers the majority of bacteria that cause brain abscess, is the most commonly used empirical regimen. Basically, the treatment of bacterial brain abscess lasts more than 6 weeks, and it is strongly recommended that patients’ clinical manifestations and brain imaging be closely monitored during the treatment. Currently, surgery combined with medical treatment, is the major therapy of brain abscess, which may reduce the duration of treatment. Conservative treatment can be adoptable under some circumstances, such as when the size of abscess is small, and condition of the patient is relatively good, etc., so that risks of invasive operation could be avoided. Unfortunately, till nowadays, there is insufficient evidence about medical treatment of bacterial brain abscess in many aspects.
Surfactin, iturin and fengycin are novel antimicrobial peptides produced mainly by Gram-positive bacilli through non-ribosome synthesis. The structure is generally composed of β-hydroxy fatty acids and 7 to 10 amino acid peptide chains linked to the amide bond peptide. With antibacterial, antifungal, antiviral, antitumoral and other biological activity, they have a good application prospect in the medical field. However, people know little about the three novel antimicrobial peptides in the field of medicine research. To solve this problem, this article describes their discovery history, structural characteristics, action mechanisms, biosynthesis and application values to provide reference for the further study.
