Rapid production of therapeutic proteins using plant system

Plant molecular farming is simply defined as the production of proteins therapeutics (PT) in plants, which involves transient gene expression in plants and purification of expressed protein to a great scale for diagnosis, treatment and other applications.  This is therapid,economical, safe and reproducible approach for the production of PTas compared to bacterial and mammalian systems. Protein yield and post-translational modifications are the major roadblocks that can be overcome byhigh expression strategies includes over expression constructs, suitable plant host systems and glycoengineering of proteins. The inherent ability of ideally producing safe, functional protein is the most striking phenomenon recognized by the pharmaceutical industries and developed many therapeutic products within few weeks to meet escalating demands during pandemic/epidemic outbreaks recentl

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation

\ua9 2023 The Authors. Published under the terms of the CC BY 4.0 license. Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in “gain-of-function” conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked cardiovascular disorders. We now report that anti-isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR-modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti-isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR-protein levels in body tissues, decreased pro-inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR-mAb mediated immune clearance of damaged isoDGR-proteins via antibody-dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age-linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders

Of mice and men: Comparative analysis of neuro-inflammatory mechanisms in human and mouse using cause-and-effect models

Perturbance in inflammatory pathways have been identified as one of the major factors which leads to neurodegenerative diseases (NDD). Owing to the limited access of human brain tissues and the immense complexity of the brain, animal models, specifically mouse models, play a key role in advancing the NDD field. However, many of these mouse models fail to reproduce the clinical manifestations and end points of the disease. NDD drugs, which passed the efficacy test in mice, were repeatedly not successful in clinical trials. There are numerous studies which are supporting and opposing the applicability of mouse models in neuroinflammation and NDD. In this paper, we assessed to what extend a mouse can mimic the cellular and molecular interactions in humans at a mechanism level. Based on our mechanistic modeling approach, we investigate the failure of a neuroinflammation targeted drug in the late phases of clinical trials based on the comparative analyses between the two species

Electricity Generation using Carboxymethyl Cellulose and Kitchen Waste as Substrate by Exiguobacterium sp SU-5 in Mediatorless Microbial Fuel Cell

Microbial fuel cell (MFC) has become a great attraction amongst most researchers, where degradation of waste takes place simultaneously produces electricity. Using an efficient organism and a better proton exchange membrane gives out good electricity. In this study, Exiguobacterium sp SU-5 was isolated from soil and used for producing electricity against carboxy methyl cellulose (CMC) in Nafion membrane and Salt bridge fitted MFC, where both act as proton exchange membrane. The organism was found to produce more electricity in Nafion membrane fitted MFC. Later the organism was subjected to produce electricity against kitchen waste and the kitchen waste was also checked for BOD, COD and other water analysis before and after the treatment. The organism could produce more electricity in Nafion membrane fitted MFC and found to reduce chloride, fluoride and hardness of water

Converting Alzheimer's disease map into a heavyweight ontology: a formal network to integrate data

International audienceAlzheimer's disease (AD) pathophysiology is still imperfectly understood and current paradigms have not led to curative outcome. Omics technologies offer great promises for improving our understanding and generating new hypotheses. However, integration and interpretation of such data pose major challenges, calling for adequate knowledge models. AlzPathway is a disease map that gives a detailed and broad account of AD pathophysiology. However, AlzPathway lacks formalism, which can lead to ambiguity and misinterpretation. Ontologies are an adequate framework to overcome this limitation, through their axiomatic definitions and logical reasoning properties. We introduce the AD Map Ontology (ADMO), an ontological upper model based on systems biology terms. We then propose to convert AlzPathway into an ontology and to integrate it into ADMO. We demonstrate that it allows one to deal with issues related to redundancy , naming, consistency, process classification and pathway relationships. Further, it opens opportunities to expand the model using elements from other resources, such as generic pathways from Reactome or clinical features contained in the ADO (AD Ontology). A version of ADMO is freely available at http://bi-oportal.bioontology.org/ontologies/ADMO

Evaluation of Antioxidant and Antimicrobial Activity of Some Plants Collected from Malaysia

Five plant species namely, Phyllanthus acidus, Piper aduncum, Pandanus amaryllifolius, Macaranga peltata and Acacia mangium were analysed for their effective in-vitro bioactivity. The chloroform and aqueous extracted of the selected plants were subjected to TLC bioautography for antioxidant activity later all the extracted were subjected for DPPH assay where the chloroform extracts were found to express maximum antioxidant property. Amongst all the plants, Macaranga peltata accounted to 95% DPPH scavenging activity. The antimicrobial studies of the plant extracts were performed via agar well diffusion method, MIC determination, Biofilm inhibition assay in microtitre plate against clinical isolates like Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. It was found that Piper aduncum (chloroform and aqueous extract) and Macaranga peltata (only aqueous) expressed antibacterial activity, of which only chloroform extract of Piper aduncum could show negative influence against the biofilm development of P.aeruginosa

Production and Utilization of SPIONs for In-vitro Drug Release and X-ray Imaging

In this study, SPIONs were produced in the presence of cobalt as catalyst. SPIONs formed by this chemical co-precipitation were size around 20 nm. After producing the SPIONs, it was subjected for functionalization with oleic acid and loaded with drug - itraconazole (a drug possess antifungal and antibacterial activity) and encapsulated with polyhydroxybutyrate (PHB). The produced core-shell SPIONS was used for antimicrobial study against two bacteria namely - Pseudomonas aeruginosa and Brevibacillus brevis and a fungi - Candida albicans. It was found to be effectively releasing drug for more than 3 hours. The SPIONs alone was acting good as contrasting agent and used for enhancing X-ray imaging