A titer for homologous viral neutralization activity (greater than 1:19,683) was observed after a 3.5-year immunization period with an octameric, branching peptide representing the principal neutralizing determinant (PND) of the human immunodeficiency virus-1IIIB envelope protein. Booster immunizations elicited persistent and potent antibodies in guinea pigs, exceeding responses produced by a conventional bovine serum albumin conjugate by 100-fold. Peptide length, central presentation of a conserved sequence, and inclusion of an upstream sequence contributed to immunogenicity. Titers (greater than 1:1,000) of heterotypic neutralizing antibodies also developed. Octameric PND peptides are a promising approach for an acquired immunodeficiency syndrome (AIDS) vaccine.
The first two authors contributed equally to this work High mobility group box Bl (HMGBl)-receptor for advanced glycation endproducts (RAGE) axis has been previously known to be involved in carcinogenesis and development of multiple malignancies. Some studies have confirmed that Ethyl pyruvate (EP), a potent inhibitor of HMGBl, exerts the therapeutic effects on metastatic live tumor from gastric cancer. However, the effects and possible molecular mechanisms of EP on gallbladder cancer (GBC) need to be further explored. In the present study, human GBC cell lines (GBC-SD and SGC-996) were treated with different concentrations of EP. Then, the expression levels of HMGBl, RAGE and some transcription factors were identified by Real-time PCR and Western blot assays. Cell proliferative activities indicated by MTT assay, invasive potential by Transwell assay and cell apoptosis and cycle distribution were performed for functional analysis of GBC cell lines in vitro. As a result, EP decreased the expression of HMGBll, RAGE, PCNA and matrix metallopeptidase-9 (MMP-9), while it increased the expression of p53. Moreover, EP administration decreased GBC cell proliferation, inhibited the invasive potential, and induced apoptosis and cycle arrest in S phase in GBC cells. In conclusion, EP administration inhibits growth and invasion of gallbladder cancer cells possibly via down-regulation of the HMGBl-RAGE axis, suggesting that EP may playa critical role in the treatment of cancer in conjunction with other therapeutic agents.High mobility group BI (HMGBI) has been known for its intracellular function as the intranuclear non-histone DNA binding protein and is regarded as an essential position in DNA repair. HMGBI and its counter-receptor, receptor for advanced glycation endproducts (RAGE), represent suitable targets for investigation, integrating many aspects of modem biology, particularly that associated with cancer (1). Originally, amphoterin, the major production of HMGB1, is over-expressed and closely associated with tumor invasion and metastasis. In human dendritic cells, RAGE is required for the effect of HMGB1 on cell expansion and survival. HMGB1/ RAGE interaction results in downstream activation of MAPK and NF-KB, representing a profitable evolutionary mechanism (2). Over-expression of HMGBI/RAGE, especially with membranous pattern, is associated with malignant potential
ABSTRACT. Human cytomegalovirus (HCMV) is a double-stranded DNA virus with the largest genome (~235 kb) of the known human herpes viruses. The coding potential and transcript structures of most HCMV predicted genes have not been identified. New or unknown genes could exist in clinical strains. The SMART (switching mechanism at 5ꞌ end of RNA template of reverse transcriptase) technique was used to construct a full-length cDNA library of an HCMV clinical strain in the late expression phase. Randomly selected clones were sequenced. The sequenced expressed sequence tags were used to identify the expression and transcript structures of some predicted and unpredicted genes of HCMV. The transcripts of the UL99, TRL5/IRL5, UL73 to UL75, UL4, and UL115 genes, which were previously detected, were obtained with full-length structures from this library. Some novel transcripts, including several transcripts of UL/b' genes and three antisense transcripts of UL83, UL87 and UL31 were found. The novel transcripts that were found, particularly the antisense transcripts of UL83, UL87 and UL31, showed that the transcription of HCMV genes is more complex than previously predicted. Our study highlights the
The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose- dependent manner the number of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.
A titer for homologous viral neutralization activity (greater than 1:19,683) was observed after a 3.5-year immunization period with an octameric, branching peptide representing the principal neutralizing determinant (PND) of the human immunodeficiency virus-1IIIB envelope protein. Booster immunizations elicited persistent and potent antibodies in guinea pigs, exceeding responses produced by a conventional bovine serum albumin conjugate by 100-fold. Peptide length, central presentation of a conserved sequence, and inclusion of an upstream sequence contributed to immunogenicity. Titers (greater than 1:1,000) of heterotypic neutralizing antibodies also developed. Octameric PND peptides are a promising approach for an acquired immunodeficiency syndrome (AIDS) vaccine.
A70-year-old retired lorry driver was admitted as an emergency with a 2-day history of moderate amount of haematemesis, nausea, vomiting and intractable hiccups. He was a known hypertensive and 5 years previously had an episode of subarachnoid haemorrhage. Complications required the insertion of a Rickman reservoir shunt. Since the time of the subarachnoid haemorrhage, his hiccups had been almost constant despite taking chlorpromazine tablets 25 mg three times a day. On examination, he had intractable hiccups. Cardiovascular, respiratory and abdominal examination were normal. Neurological examination revealed a right-sided partial third nerve palsy (with ptosis and pupillary sparing). He also had a right-sided squint operation during childhood. More detailed examination of the cranial nerves revealed mild right-sided glossopharyngeal and hypoglossal nerve palsies. Routine full blood count, blood biochemistry, chest X-ray and abdominal ultrasound scan were normal. Upper gastrointestinal endoscopy revealed a hiatus hernia with mild oesophagitis. He was started on omeprazole. In view of the neurological findings and past history of subarachnoid bleed, a magnetic resonance imaging brain scan was performed. This revealed a large basilar artery aneurysm with a significant mass effect on the brainstem at the level of the border of fourth ventricle (Figures 1–3). Alternative drug treatment in the form of nifedipine 10 mg three times a day was initiated instead of chlorpromazine and the hiccups resolved completely. On follow-up in the clinic a few months later, there was no recurrence of the hiccups.
Seedlings of Suaeda ussuriensis were grown in soil with NaCl concentrations of 0.5, 1.0, 2.0 and 3.0% on a dry weight basis. The optimum salt concentration for growth and development was 1.0%. At 3.0% all seedlings died. Treatment with 10*5 �g/litre GA3 counteracted partly the growth inhibition, and the dry weight of plants increased 21.6, 2.2 and 19.4%, respectively, for soils with salt concentrations of 0.5, 1.0 and 2.0%. GA*3 increased the numbers of plants coming to flower in soil of salt concentration of 0.5 and 2.0%, by 40 and 20%, respectively, but had no effect on plant growth in a salt concentration of 1.0%.
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