PMID: 

Hum Vaccin Immunother. 2015 ;11(4):998-1009. PMID: 25803132

Abstract Title: 

Characteristics and viral propagation properties of a new human diploid cell line, Walvax-2, and its suitability as a candidate cell substrate for vaccine production.

Abstract: 

Human diploid cell strains (HDCSs), possessing identical chromosome sets known to be free of all known adventitious agents, are of great use in developing human vaccines. However it is extremely difficult to obtain qualified HDCSs that can satisfy the requirements for the mass production of vaccines. We have developed a new HDCS, Walvax-2, which we derived from the lung tissue of a 3-month-old fetus. We established primary, master and working cell banks successfully from reconstituted frozen cells. Observations during the concurrent propagation of Walvax-2 and MRC-5 cells revealed differences in terms of growth rate, cell viability and viral sensitivities. Specifically, Walvax-2 cells replicated more rapidly than MRC-5 cells, with Walvax-2 cells attaining the same degree of confluence in 48 hours as was reached by MRC-5 cells in 72 hours. Moreover, Walvax-2 cells attained 58 passages of cell doublings whereas MRC-5 reached 48 passages during this period. We also assessed the susceptibility of these cells to rabies, hepatitis A, and Varicella viruses. Analysis of virus titers showed the Walvax-2 cells to be equal or superior to MRC-5 cells for cultivating these viruses. Furthermore, in order to characterize the Walvax-2 cell banks, a series of tests including cell identification, chromosomal characterization, tumorigenicity, as well as tests for the presence of microbial agents, exogenous viruses, and retroviruses, were conducted according to standard international protocols. In conclusion, results from this study show that Walvax-2 cell banks are a promising cell substrate and could potentially be used for the manufacturing of HDCVs.

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PMID: 

BMJ Case Rep. 2018 Mar 22 ;2018. Epub 2018 Mar 22. PMID: 29572367

Abstract Title: 

Myocarditis secondary to smallpox vaccination.

Abstract: 

The development of vaccines ushered in the most profound advancement in 20th century medicine, and have widely been regarded as the one of the most important scientific discovery in the history of mankind. However, vaccines are not without risk; reactions can range from injection site reactions to life-threatening anaphylaxis. Among the more serious vaccine-related sequela is myocarditis. Although myocarditis has been reported following many different vaccines, the smallpox vaccine has the strongest association. We report a case of a 36-year-old active duty service member presenting with progressive dyspnoea, substernal chest pain and lower extremity swelling 5 weeks after receiving the vaccinia vaccination. The aetiology of his acute decompensated heart failure was determined to be from myocarditis. Although the majority of cases of myocarditis resolve completely, some patients develop chronic heart failure and even death. Vaccine-associated myocarditis should always be on the differential for patients that exhibit cardiopulmonary symptoms after recent vaccinations.

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PMID: 

Am J Pathol. 2000 Jun ;156(6):2057-65. PMID: 10854227

Abstract Title: 

The endogenous adjuvant squalene can induce a chronic T-cell-mediated arthritis in rats.

Abstract: 

Squalene is a cholesterol precursor, which stimulates the immune system nonspecifically. We demonstrate that one intradermal injection of this adjuvant lipid can induce joint-specific inflammation in arthritis-prone DA rats. Histopathological and immunohistochemical analyses revealed erosion of bone and cartilage, and that development of polyarthritis coincided with infiltration of alphabeta(+) T cells. Depletion of these cells with anti-alphabeta TcR monoclonal antibody (R73) resulted in complete recovery, whereas anti-CD8 and anti-gammadelta TcR injections were ineffective. The apparent dependence on CD4(+) T cells suggested a role for genes within the major histocompatibility complex (MHC), and this was concluded from comparative studies of MHC congenic rat strains, in which DA.1H rats were less susceptible than DA rats. Furthermore, LEW.1AV1 and PVG.1AV1 rats with MHC identical to DA rats were arthritis-resistant, demonstrating that non-MHC genes also determine susceptibility. Some of these genetic influences could be linked to previously described arthritis susceptibility loci in an F2 intercross between DA and LEW.1AV1 rats (ie, Cia3, Oia2 and Cia5). Interestingly, some F2 hybrid rats developed chronic arthritis, a phenotype not apparent in the parental inbred strains. Our demonstration that an autoadjuvant can trigger chronic, immune-mediated joint-specific inflammation may give clues to the pathogenesis of rheumatoid arthritis, and it raises new questions concerning the role of endogenous molecules with adjuvant properties in chronic inflammatory diseases.

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PMID: 

Wien Klin Wochenschr. 2013 Feb ;125(3-4):61-70. Epub 2013 Jan 19. PMID: 23334477

Abstract Title: 

Neurotoxic effects of nonylphenol: a review.

Abstract: 

Nonylphenol (NP), identified as an environmental endocrine disruptor, used as important raw materials for detergents, emulsifiers, and wetting agents in industry and is also found in paints, pesticides, and household toiletries. NP has been reported to have deleterious effects on central nervous system (CNS) other than reproductive and immune systems including disrupting neuroendocrine homeostasis, altering cognitive function, and neurotoxicity of tissues, etc., particularly when NP's disruption occurs during critical developmental window of brain. This review will discuss the evidence for environmental endocrine disruption of NP and the sequelae on endocrine, reproductive and nerve functions, as well as causal relationships between endocrine disruption and cognitive behavior effects.

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PMID: 

J Clin Med. 2019 Aug 7 ;8(8). Epub 2019 Aug 7. PMID: 31394821

Abstract Title: 

The Effect of Dietary Supplementation of Crocetin for Myopia Control in Children: A Randomized Clinical Trial.

Abstract: 

The prevalence of myopia has been increasing in recent years. The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. We evaluated the effects of crocetin on myopia suppression in children. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between -1.5 and -4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks. Both written informed assent from the participants and written informed consent from legal guardians were obtained in this study because the selection criteria of this trial included children aged between 6 and 12 years old. This trial was approved by the institutional review boards. A mixed-effects model was used for analysis, using both eyes. Two participants dropped out and 67 children completed this trial. The change in SER in the placebo group, -0.41± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, -0.33 ± 0.05 D (= 0.049). The AL elongation in the placebo group, 0.21± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (= 0.046). In conclusion, dietary crocetin may have a suppressive effect on myopia progression in children, but large-scale studies are required in order to confirm this effect.

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PMID: 

Bull Exp Biol Med. 2008 Feb ;145(2):259-62. PMID: 19023984

Abstract Title: 

Antiparkinsonian effect of nerve growth factor adsorbed on polybutylcyanoacrylate nanoparticles coated with polysorbate-80.

Abstract: 

The study examined the antiparkinsonian effect of nerve growth factor adsorbed on the surface of polybutylcyanoacrylate nanoparticles coated with polysorbate-80 surfactant. The parkinsonian syndrome in C57B1/6 mice was provoked by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The basic symptoms of the parkinsonian syndrome decreased under the action of the nerve growth factor adsorbed on nanoparticles coated with polysorbate-80, which was seen from decreased rigidity and increased locomotor activity compared to control mice receiving with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone. This effect of nerve growth factor on nanoparticles persisted after 7 and 21 days after single injection of the neurotoxin. These data attest to the possibility of using nanoparticles prepared from amphiphilic polymers and coated with polysorbate-80 for the delivery of nerve growth factor into the brain during systemic treatment.

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PMID: 

J Microencapsul. 2016 Nov ;33(7):646-655. Epub 2016 Oct 14. PMID: 27682805

Abstract Title: 

Polysorbate-80-coated, polymeric curcumin nanoparticles for in vivo anti-depressant activity across BBB and envisaged biomolecular mechanism of action through a proposed pharmacophore model.

Abstract: 

Depression is a modern world epidemic. Its main causative factor is oxidative stress, as reported in study subjects. Natural products are yet to show significant therapeutic effects in comparison with synthetic drugs. Current study deals with the preparation of brain-targeted polysorbate-80-coated curcumin PLGA nanoparticles (PS-80-CUR-NP), and their characterisation via Spectral and optical methods. PS-80-CUR-NP were evaluated against the oxidative stress-mediated depressant (OSMD) activity via Force despair, Tail suspension tests and stress biomarker assay (SOD and catalase activity). A significant reduction in immobility (p 

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PMID: 

ACS Appl Mater Interfaces. 2016 05 11 ;8(18):11336-41. Epub 2016 Apr 27. PMID: 27092793

Abstract Title: 

Superparamagnetic Iron Oxide Nanoparticles Modified with Tween 80 Pass through the Intact Blood-Brain Barrier in Rats under Magnetic Field.

Abstract: 

The methods for the delivery of theranostic agents across the blood-brain barrier (BBB) are highly required. Superparamagnetic iron oxide nanoparticles (SPIONs) coated with PEG (poly(ethylene glycol)), PEI (poly(ethylene imine)), and Tween 80 (polysorbate 80) (Tween-SPIONs) were prepared. We demonstrate the effective passage of tail-vein-injected Tween-SPIONs across normal BBB in rats under an external magnetic field (EMF). The quantitative analyses show significant accumulation of SPIONs in the cortex near the magnet, with progressively lower accumulation in brain tissues far from the magnet. A transmission electron microscopy picture of an ultrathin section of the rat brain displays Tween-SPIONs crossing the BBB. The comparative study confirms that both the Tween-80 modification and EMF play crucial roles in the effective passage of SPIONs across the intact BBB. However, the magnetic force alone cannot drag the SPIONs coated with PEI/PEG polymers through the BBB. The results indicate the Tween-SPIONs cross the BBB via an active penetration facilitated by EMF. This work is encouraging for further study on the delivery of drug or diagnostic agents into the parenchyma of the brain for dealing with neurological disorders by using Tween-SPIONs carriers under EMF.

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PMID: 

NeuroRx. 2005 Jan ;2(1):3-14. PMID: 15717053

Abstract Title: 

The blood-brain barrier: bottleneck in brain drug development.

Abstract: 

The blood-brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain approximately 100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. Despite the importance of the BBB to the neurotherapeutics mission, the BBB receives insufficient attention in either academic neuroscience or industry programs. The combination of so little effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential CNS drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders. This situation can be reversed by an accelerated effort to develop a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain capillary endothelium. This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences.

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PMID: 

Environ Int. 2016 Mar ;88:288-298. Epub 2016 Jan 28. PMID: 26826339

Abstract Title: 

Environmental factors in the development of autism spectrum disorders.

Abstract: 

Autism spectrum disorders (ASD) are highly heterogeneous developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior and repetitive movements. Social interaction impairments are the most characteristic deficits in ASD. There is also evidence of impoverished language and empathy, a profound inability to use standard nonverbal behaviors (eye contact, affective expression) to regulate social interactions with others, difficulties in showing empathy, failure to share enjoyment, interests and achievements with others, and a lack of social and emotional reciprocity. In developed countries, it is now reported that 1%-1.5% of children have ASD, and in the US 2015 CDC reports that approximately one in 45 children suffer from ASD. Despite the intense research focus on ASD in the last decade, the underlying etiology remains unknown. Genetic research involving twins and family studies strongly supports a significant contribution of environmental factors in addition to genetic factors in ASD etiology. A comprehensive literature search has implicated several environmental factors associated with the development of ASD. These include pesticides, phthalates, polychlorinated biphenyls, solvents, air pollutants, fragrances, glyphosate and heavy metals, especially aluminum used in vaccines as adjuvant. Importantly, the majority of these toxicants are some of the most common ingredients in cosmetics and herbicides to which almost all of us are regularly exposed to in the form of fragrances, face makeup, cologne, air fresheners, food flavors, detergents, insecticides and herbicides. In this review we describe various scientific data to show the role of environmental factors in ASD.

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