A monoclonal antibody identifies a 215 000-dalton nuclear envelope protein restricted to certain cell types

The monoclonal antibody, AGF2.3, was isolated from mice immunised with the human promyeloid cell line HL60. By immunofluorescence and immunoelectron microscopy the antibody was shown to bind to the nuclear envelope in uninduced HL60 cells. Immunofluorescent staining was reduced to very low levels in HL60 cells induced to mature to monocytes or neutrophils by addition of 12-0-tetradecanoylphorbol-13-acetate or dimethyl sulfoxide respectively. Blood neutrophils did not express the antigen. Weak immunofluorescent staining of cell nuclei was observed in peripheral blood lymphocytes and in sections of normal human kidney, tonsil and skin epithelium. The AGF2.3 antigen was strongly expressed on the nuclei of 21/21 haemopoietic cell lines and 21/25 permanent non-haemopoietic cell lines representing various cell types. In contrast, the antigen was not expressed by any of six primary (untransformed) cell cultures. These included fibroblasts, endothelial cells and keratinocytes. The antigen was expressed in the Q10 SV-40 transformed cell line derived from a non-expressing primary fibroblast culture. AGF2.3 antibody precipitated a protein with an apparent subunit molecular weight of approximately 215 kDa from Triton X-100 extracts of HL60 and HeLa cells labelled with 35S-methionine. This protein was not detectable in extracts of primary skin fibroblasts prepared in parallel. We conclude that AGF2.3 antibody recognises a previously undescribed protein associated with the nuclear envelope which is expressed at high levels in most transformed cell lines but which is weakly expressed or absent in normal tissues and primary cell cultures.     

Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood–brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6?nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.     

Analysis of mechanical parameters on the thromboembolism using a patient-specific computational model

Ischemic stroke is a major cause of death and long-term disabilities worldwide. In this paper, we aim to represent a comprehensive simulation of the motion of emboli through cerebrovascular network within patient-specific computational model. The model consists of major arteries of the circle of Willis reconstructed from magnetic resonance angiography images, pulsatile flow and emboli with different sizes and material properties. Here, the fluid–structure interactions method was used to simulate the motion of deformable and rigid emboli through cerebral arteries. Hemodynamic changes in the circle of Willis due to the entrance of embolus are observed. The effect of material properties on the distribution ratio and dynamics of motion of the emboli in the cerebral arterial network is also analyzed. Our results reveal that as the rigidity of emboli increases, higher proportion of them tend to enter to the larger arteries (e.g., middle cerebral artery). Scrutinizing the amount of stress acting on the emboli represented in this paper can broaden our understanding of the rheological phenomenon (e.g., lysis or growth of emboli during embolism). The approach of considering different material properties of the thrombus in a patient-specific computational model not only enable us to better understand the roll of biomechanical parameters causing the embolism, but also lead to a better clinical decision making to manage patients with stroke.     

Investigating the role of T helper related cytokines in cerebrospinal fluid for the differential diagnosis of bacterial meningitis in pre-treated paediatric patients

Abstract

Purpose: Given the challenge in the diagnosis of bacterial meningitis (BM), we assessed different cytokines in the cerebrospinal fluid (CSF) of antibiotics pre-treated patients.

Materials and methods: Laboratory tests and polymerase chain reaction (PCR) were performed for 480 CSF samples from children (2 m to 14 y), suspicious to meningitis and pre-treated with antibiotics, to detect bacterial and viral aetiologies. Sixty-one CSF were included and the levels of 13 cytokines such as IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α were measured using flow-cytometry.

Results: All bacterial cultures were negative, but 29 and eight CSF were positive for bacterial and viral agents by PCR. IL-6, IL-10 and IFN-γ were significantly up-regulated in BM. T helper (Th) subset cytokines showed significant upregulation of Th1, Th2, Th17, Th22 and Tfh cytokines in BM. Common Th subsets cytokines (IL-6, IL-10 and TNF-α) were significantly different between the study groups. ROC curve analysis revealed good AUC for common Th related cytokines in discriminating BM.

Conclusions: In pre-treated BM patients with negative bacterial cultures, cytokines IL-6, IL-10 and IFN-γ can predict BM which could be beneficial for rapid diagnosis and treatment to decrease the sequela of the disease.     

Efficient and reliable propagation and rooting of foetid juniper (Juniperus foetidissima Willd.), as an endangered plant under in vitro condition

In Vitro Cellular & Developmental Biology - Plant - Foetid juniper (Juniperus foetidissima Willd.) is one of the most important coniferous species faced with multiple threats and it is...     

A global treatments for coronaviruses including COVID-19

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.     

Anti-CD37 targeted immunotherapy of B-Cell malignancies

CD37 is a member of tetra-spanning superfamily (characterized by their four transmembrane domains). It is one of the specific proteins for normal and malignant mature B cells. Anti CD37 monoclonal antibodies are reported to improve the overall survival in CLL. These therapeutics will increase the efficacy and reduce the toxicity in patients with both newly diagnosed and relapsed and refractory disease. Recent clinical trials have shown promising outcomes for these agents, administered both as monotherapy and in combination with standard chemotherapeutics. Long-term follow-up of combination regimens has even raised the question of whether the patients with CLL could be treated with intensive chemo-immunotherapy. In the present study, CD37 is introduced as an appealing target to treat B cell malignancies. The anti-CD37 antibodies as one of the most successful therapeutics against CD37 are introduced and the clinical outcomes of their exploitation are explained.