Developing Protein-Based Nanoparticles as Versatile Delivery Systems for Cancer Therapy and Imaging.

In recent years, it has become apparent that cancer nanomedicine's reliance on synthetic nanoparticles as drug delivery systems has resulted in limited clinical outcomes. This is mostly due to a poor understanding of their "bio-nano" interactions. Protein-based nanoparticles (PNPs) are rapidly emerging as versatile vehicles for the delivery of therapeutic and diagnostic agents, offering a potential alternative to synthetic nanoparticles. PNPs are abundant in nature, genetically and chemically modifiable, monodisperse, biocompatible, and biodegradable. To harness their full clinical potential, it is important for PNPs to be accurately designed and engineered. In this review, we outline the recent advancements and applications of PNPs in cancer nanomedicine. We also discuss the future directions for PNP research and what challenges must be overcome to ensure their translation into the clinic

Toxoplasmosis in Zoo Animals

Toxoplasma gondii is an extremely successful zoonotic protozoan parasite that has been demonstrated in a wide range of endo- and poikilothermic species. Although infection is widespread amongst domestic animals, overt disease other than abortion in small ruminants is sporadic. This survey evaluates toxoplasmosis in zoo animals based on a systematic review of pathology archive material (n = 33,506 submissions) over a 16-year study period. A total of 126 submissions, deriving from 32 zoos, two educational facilities and two private owners, were included in the study, based on gross lesions, cytological, histological and immunohistological diagnosis of toxoplasmosis. Clinical history, signalment, annual distribution and post-mortem findings were evaluated. A total of 31 species (mammalian 97%/avian 3%) were represented in the study material. Ring-tailed lemurs, slender tailed meerkats, Pallas’ cats, and squirrel monkeys were most affected. An unusual outbreak occurred in Asian small-clawed otters, in which toxoplasmosis has not been reported to date. Clinically, animals over 12 months of age presented with non-specific symptoms (anorexia, weight loss, lethargy, debilitation), neurological, gastrointestinal or respiratory signs and sudden death. Systemic disease predominated, with a propensity for encephalitis in meerkats and Pallas’ cats and systemic disease involving lymphoid tissues in ring-tailed lemurs. Cases in the UK occurred year-round, with species-specific peaks and increases between August and November. This study reinforces the importance of toxoplasmosis as a significant cause of sporadic and epizootic mortalities in a wide range of zoo animals. Feral cat control is crucial to reduce infection pressure

Novel Carbyne Filled Carbon Nanotube – Polymer Nanocomposites

The availability of carbyne in carbon nanotubes (CNTs) induces intrinsic stiffening and strengthening of CNTs, and is exploited for the very first time in this report to process epoxy nanocomposites with improved mechanical and electrical properties. The existence of encapsulated carbyne in double wall CNTs (DWNTs) was confirmed using High Resolution Transmission Electron Microscopy (HR-TEM). The intrinsic stiffening of carbyne reinforced DWNTs (c-DWNTs) in epoxy matrix was visually confirmed by Field Emission Scanning Electron Microscopy (FE-SEM). In comparison to raw DWNTs reinforced epoxy nanocomposites, c-DWNTS imparted modest but improved tensile strength (5.6%), elastic modulus (9.7%), failure strain (9.9%) and fracture toughness (13%) to their respective epoxy nanocomposites. This inaugural study on carbyne-filled polymer composites also reports a minor but distinct increase (an order of magnitude) in the electrical conductivity for c-DWNTs filled epoxy nanocomposites compared to DWNT filled epoxy nanocomposites

Antioxidant Activity and Inhibitory Effect of Some Commonly used Medicinal Plants against Lipid Per-Oxidation in Mice Brain

Background: The present study compares the protective properties of aqueous extracts of six medicinal plants, Phyllanthus emblica, Terminaliachebula (black and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against lipid per-oxidation in mice brain.Methods: The antioxidant activities were analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, total antioxidantactivity and metal chelation.Results: The extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive species (TBARS) induced by pro-oxidant (10 µM FeSO4) in mice brain. Moreover, the free radical scavenging activities of the extracts was evaluated by the scavenging of DPPH radical (IC50, 23.23±1.2 µg/ml (Phyllanthus emblica), 20.24±0.9 µg/ml (Terminalia chebula yellow) and 17.33±1.1 µg/ml (Terminalia chebula black), 19.44±0.45 µg/ml (Terminalia arjuna), 56.59±2.1 µg/ml (Balsamodendron Mukul) and . 200 µg/ml (Alium sativum).Conclusion: The higher antioxidant and inhibitory effect of Terminalia chebula black in this study could be attributed to its significantly higherphenolic content, Fe(II) chelating ability, reducing ability and free radical scavenging activity. Therefore oxidative stress in brain could be potentiallyprevented by the intake of these plants.Key words: Antioxidant activity, Balb c mice, iron chelation, phenolics, oxidative stress, medicinal plants

Can retail investors induce corporate green innovation? -Evidence from Baidu Search Index

China's rapid economic development has caused some environmental damage in recent years. The popularity of the Internet has enriched the ways for investors to obtain information, which would exert an impact on corporate environmental behavior. Focusing on micro-enterprise green innovation from the perspective of informal regulation, this paper investigates the impact of investor attention on corporate green innovation. This study takes Chinese A-share listed companies from 2011 to 2018 as samples, constructs panel fixed-effects models and adopts multiple linear, Logistic and Tobit regressions. This article finds that investor attention, measured by the web search index, can significantly improve corporate green innovation. The conclusion is still valid after a series of robust tests. Besides, mechanism tests reveal that investor attention can promote corporate green innovation by improving the implementation efficiency of punitive environmental regulation, the use efficiency of environmental subsidies, and by increasing the reputation cost of enterprises. In additional tests, this paper further clarifies that investors' attention to negative public opinion can play a better role in environmental governance, and reveals the reason why investors are motivated to improve corporate green innovation. This research puts forward a unique perspective, which extends the understanding of informal environmental regulation and enriches research on green innovation at the micro-enterprise level, promoting the cross research of finance and environmental protection. © 2022 The Author(s

Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles

This work is licensed under a Creative Commons Attribution 4.0 International License.The macrocyclic tetrapeptide cyclo[Phe-d-Pro-Phe-Trp] (CJ-15,208) and its stereoisomer cyclo[Phe-d-Pro-Phe-d-Trp] exhibit different opioid activity profiles in vivo. The present study evaluated the influence of the Phe residues’ stereochemistry on the peptides’ opioid activity. Five stereoisomers were synthesized by a combination of solid-phase peptide synthesis and cyclization in solution. The analogs were evaluated in vitro for opioid receptor affinity in radioligand competition binding assays, and for opioid activity and selectivity in vivo in the mouse 55 °C warm-water tail-withdrawal assay. Potential liabilities of locomotor impairment, respiratory depression, acute tolerance development, and place conditioning were also assessed in vivo. All of the stereoisomers exhibited antinociception following either intracerebroventricular or oral administration differentially mediated by multiple opioid receptors, with kappa opioid receptor (KOR) activity contributing for all of the peptides. However, unlike the parent peptides, KOR antagonism was exhibited by only one stereoisomer, while another isomer produced DOR antagonism. The stereoisomers of CJ-15,208 lacked significant respiratory effects, while the [d-Trp]CJ-15,208 stereoisomers did not elicit antinociceptive tolerance. Two isomers, cyclo[d-Phe-d-Pro-d-Phe-Trp] (3) and cyclo[Phe-d-Pro-d-Phe-d-Trp] (5), did not elicit either preference or aversion in a conditioned place preference assay. Collectively, these stereoisomers represent new lead compounds for further investigation in the development of safer opioid analgesics.National Institute on Drug Abuse (R01 DA18832)National Institute on Drug Abuse (R01 DA032928

Down-regulation of IRES containing 5'UTR of HCV genotype 3a using siRNAs

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major causative agent of liver associated diseases leading to the development of hepatocellular carcinoma (HCC) all over the world and genotype-3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current chemotherapy of interferon-α (IFN-α) and ribavirin against HCV infection alternative options are desperately needed out of which the recently discovered RNAi represent a powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process to silence virus infection or replication. HCV translation is mediated by a highly conserved internal ribosome entry site (IRES) within the 5'UTR region making it a relevant target for new drug development.</p> <p>Materials and methods</p> <p>The present study was proposed to assess and explore the possibility of HCV silencing using siRNA targeting 5'UTR. For this analysis full length HCV 5'UTR of HCV-3a (pCR3.1/5'UTR) was tagged with GFP protein for <it>in vitro </it>analysis in Huh-7 cells. siRNA targeting 5'UTR were designed, and tested against constructed vector in Huh-7 cell line both at RNA and Protein levels. Furthermore, the effect of these siRNAs was confirmed in HCV-3a serum infected Huh-7 cell line.</p> <p>Results</p> <p>The expression of 5'UTR-GFP was dramatically reduced both at mRNA and protein levels as compared with Mock transfected and control siRNAs treated cells using siRNAs against IRES of HCV-3a genotype. The potential of siRNAs specificity to inhibit HCV-3a replication in serum-infected Huh-7 cells was also investigated; upon treatment with siRNAs a significant decrease in HCV viral copy number and protein expression was observed.</p> <p>Conclusions</p> <p>Overall, the present work of siRNAs against HCV 5'UTR inhibits HCV-3a expression and represents effective future therapeutic opportunities against HCV-3a genotype.</p

Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.

Chenopodium murale L. is an invasive weed species significantly interfering with wheat crop. However, the complete nature of its allelopathic influence on crops is not yet fully understood. In the present study, the focus is made on establishing the relation between plant morphophysiological changes and oxidative stress, induced by allelopathic extract. Phytotoxic medium of C. murale hairy root clone R5 reduced the germination rate (24% less than control value) of wheat cv. Nataša seeds, as well as seedling growth, diminishing shoot and root length significantly, decreased total chlorophyll content, and induced abnormal root gravitropism. The R5 treatment caused cellular structural abnormalities, reflecting on the root and leaf cell shape and organization. These abnormalities mostly included the increased number of mitochondria and reorganization of the vacuolar compartment, changes in nucleus shape, and chloroplast organization and distribution. The most significant structural changes were observed in cell wall in the form of amoeboid protrusions and folds leading to its irregular shape. These structural alterations were accompanied by an oxidative stress in tissues of treated wheat seedlings, reflected as increased level of H2O2 and other ROS molecules, an increase of radical scavenging capacity and total phenolic content. Accordingly, the retardation of wheat seedling growth by C. murale allelochemicals may represent a consequence of complex activity involving both cell structure alteration and physiological processes.This is a post-peer-review, pre-copyedit version of an article published in Protoplasma. The final authenticated version is available online at: [http://dx.doi.org/10.1007/s00709-018-1250-0

Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial

Introduction: Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective. Method and analysis: A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process. Ethics and dissemination: Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals. Trial registration number: NCT04131179