PMID: 

Vaccine. 2019 Sep 20 ;37(40):5986-5993. Epub 2019 Aug 23. PMID: 31451326

Abstract Title: 

The mad leading the blind: Perceptions of the vaccine-refusal movement among Australians who support vaccination.

Abstract: 

BACKGROUND: Vaccine refusal is shaped by the social ecology in which it occurs. How people who refuse vaccines are communicated to and treated may affect the nature and strength of their negative vaccine beliefs, and their responsiveness to health promotion messages. Yet little is known about how people who refuse vaccines are perceived by the public. Our research examined perceptions among pro-vaccine Australians of the vaccine-refusal movement.METHODS: Descriptions of the vaccine-refusal movement by 2666 pro-vaccine Australians were analysed using thematic discourse analysis. Descriptive themes were identified via inductive, iterative coding. Discourse analysis techniques were then used to interpret latent beliefs about the vaccine-refusal movement.RESULTS: Participants had negative and stigmatising perceptions of the vaccine-refusal movement. They believed the movement is dangerous, misinformed, and comprised of charlatans and fools who are unintelligent, selfish, overly emotional, conspiratorial and scientifically illiterate. Discursive analysis showed that these perceptions were underpinned by beliefs that people would have to be defective in some way to believe anti-vaccine rhetoric. Furthermore, perceptions were underpinned by beliefs that the movement spreads not only disease, but also dangerous ideas that were seen to attack the social order, institutions, values and reason. Participants' intensely-negative views related to their inability to imagine why someone would refuse vaccines.CONCLUSIONS: This research provides a focused, qualitative account of public perceptions of the vaccine-refusal movement. The findings are concerning: stigma towards vaccine-refusing people may adversely affect their wellbeing and entrench their negative vaccine beliefs. The research suggests that more compassionate, nuanced discussion of vaccine refusal in the public sphere is needed. It also supports the need to systematically examine public attitudes towards vaccine refusal as a determinant of vaccine confidence.

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PMID: 

Vaccine. 2019 Sep 24 ;37(41):6093-6101. Epub 2019 Aug 27. PMID: 31471145

Abstract Title: 

The cost saving opportunity of introducing a card review into measles-containing vaccination campaigns.

Abstract: 

Measles vaccination is a cost-effective way to prevent infection and reduce mortality and morbidity. However, in countries with fragile routine immunization infrastructure, coverage rates are still low and supplementary immunization campaigns (SIAs) are used to reach previously unvaccinated children. During campaigns, vaccine is generally administered to every child, regardless of their vaccination status and as a result, there is the possibility that a child that is already immune to measles (i.e. who has had 2+ vaccinations) would receive an unnecessary dose, resulting in excess cost. Selective vaccination has been proposed as one solution to this; children who were able to provide documentation of previous vaccination would not be vaccinated repeatedly. While this would result in reduced vaccine and supply cost, it would also require additional staff time and increased social mobilization investment, potentially outweighing the benefits. We utilize Monte Carlo simulation to assess under what conditions a selective vaccination policy would indeed result in net savings. We demonstrate that cost savings are possible in contexts with a high joint probability of an individual child having both 2+ previous measles doses and also an available record. We also find that the magnitude of net cost savings is highly dependent on whether a country is using measles-only or measles-rubella vaccine and on the required skill set of the individual who would review the previous vaccination records.

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PMID: 

Vaccine. 2019 Sep 30 ;37(42):6201-6207. Epub 2019 Sep 5. PMID: 31495592

Abstract Title: 

Phase 1 trial of a 20-valent pneumococcal conjugate vaccine in healthy adults.

Abstract: 

INTRODUCTION: Streptococcus pneumoniae is a leading cause of bacteremia, bacterial pneumonia, and meningitis, and is associated with substantial morbidity and mortality, particularly in those under 2 years of age and those over 65 years of age. While significant progress against S. pneumoniae-related disease has been made as a result of the introduction of pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13), there remains value in further expanding pneumococcal vaccine serotype coverage. Here we present the first report of a 20-valent pneumococcal conjugate vaccine (PCV20) containing capsular polysaccharide conjugates present in PCV13 as well as 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) which are important contributors to pneumococcal disease.METHODS: This Phase I first-in-human study was a randomized, controlled, observer-blinded study with a two-arm parallel design to assess the safety, tolerability, and immunogenicity of PCV20 in adults. A total of 66 healthy adults 18-49 years of age with no history of pneumococcal vaccination were enrolled and randomized to receive a single dose of PCV20 or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) control. Local injection site reactions, select systemic symptoms, laboratory studies, and adverse events were assessed. Opsonophagocytic activity (OPA) titers and IgG concentrations were measured in sera collected prior to, and approximately one month (28-35 days) after vaccination.RESULTS: Vaccination with PCV20 elicited substantial IgG and functional bactericidal immune responses as demonstrated by increases in IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) to the 20 vaccine serotypes. The overall safety profile of PCV20 was similar to Tdap, and generally consistent with that observed after PCV13 administration.CONCLUSIONS: Vaccination with PCV20 was well tolerated and induced substantial functional (OPA) and IgG responses to all vaccine serotypes. There were no safety issues identified in this Phase 1 study, and the data supported further evaluation of PCV20.

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PMID: 

Vaccine. 2019 Sep 30 ;37(42):6144-6153. Epub 2019 Sep 4. PMID: 31493949

Abstract Title: 

Clinical trials with GMO-containing vaccines in Europe: Status and regulatory framework.

Abstract: 

Recombinant technology has revolutionised the way novel vaccines are developed and manufactured. The possibility to genetically modify micro-organisms to bring immunogenic material (antigens/epitopes) to the human (or animal) immune system to provoke an immune response, provides new hope to producing prophylactic vaccines against HIV, malaria and tuberculosis and emerging diseases. Regulatory requirements associated with the development of genetically-modified organism (GMO)-containing vaccines in Europe add an additional burden to the clinical trial application procedure and to the preparation and initiation of a clinical trial of such vaccines. Moreover, the GMO regulatory framework is complex and only partially harmonised across Europe, which may hamper multi-country clinical trials with GMO-containing vaccines. This paper provides an overview of clinical trial applications with GMO-containing vaccines in Europe and reviews the regulatory framework in countries where GMO-containing vaccine clinical trial authorisation (CTA) applications were submitted between 2004 and 2017.

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PMID: 

J Ethnopharmacol. 2020 Jan 10 ;246:112242. Epub 2019 Sep 15. PMID: 31533077

Abstract Title: 

Musa acuminata and its bioactive metabolite 5-Hydroxymethylfurfural mitigates quorum sensing (las and rhl) mediated biofilm and virulence production of nosocomial pathogen Pseudomonas aeruginosa in vitro.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Musa acuminata, a tropical plant belongs to the family Musaceae. The fruit peels of this plant have been well documented for their therapeutic value in Asia and Africa. It has also been previously reported for numerous biological applications such as antimicrobial, antioxidant, itching, psoriasis and anti-diarrheal activities. Moreover, M. acuminata peels have been well known for its anti-healing and antiseptic properties and most commonly used for healing wounds and heat burns in South Asian and African traditional medicines.AIM OF THE STUDY: To evaluate the QS-mediated antibiofilm and antivirulence potential of M. acuminata, and its bioactive metabolites 5-Hydroxymethylfurfural (5HMF) against Pseudomonas aeruginosa.MATERIALS AND METHODS: The M. acuminata peel methanol extract (MAM) was evaluated for its antibiofilm potential against P. aeruginosa with increasing concentration. Besides, biofilm related phenomenon's such as total biofilm proteins, microcolony formation exopolysaccharides (EPS) and cell surface hydrophobicity (CSH) productions were also examined to support the antibiofilm potential of MAM. Further, MAM was evaluated for its antivirulence efficacy against P. aeruginosa by assessing the protease, LasA protease, LasB elastase, pyocyanin, alginate and rhamnolipid productions at 400 μg mlconcentration. Transcriptional analysis of QS regulated virulence genes expression level was also done by real-time PCR analysis. Then, the MAM was subjected to column chromatography for further fractions and the bioactive compounds present in MAM were identified by gas chromatograph-mass spectrometry analysis. Further, the major compounds such as 5-hydroxymethylfurfural, vaccenic acid and pentanoic acid identified from active fraction of MAM were evaluated for their antibiofilm and antivirulence potential against P. aeruginosa.RESULTS: MAM significantly inhibited the biofilm formation in P. aeruginosa at 400 μg mlconcentration which also inhibited the production of biofilm proteins, biofilm adherence, EPS and CSH productions to the level of 79%, 82% and 77% respectively. Further, the antivirulence potential was confirmed through numerous virulence inhibition assays. The MAM at 400 μg mlconcentration inhibited the QS-mediated virulence production such as protease, LasA protease, LasB elastase, pyocyanin, alginate and rhamnolipid productions to the level of 77%, 75%, 68%, 80%, 78% and 69% respectively. Moreover, the results of qPCR analysis confirmed the downregulation of QS regulated virulence genes expression upon treatment with MAM. The chromatographic analysis revealed the presence of 5-Hydroxymethylfurfural (5HMF), vaccenic acid and pentanoic acid in MAM and the potential bioactive compounds with antibiofilm and antivirulence was identified as 5-hydroxymethylfurfural, without exerting any growth inhibition in P. aeruginosa.CONCLUSION: This study investigated the ideal antibiofilm and antivirulence potential of MAM and its bioactive compound 5HMF, and confirms the ethnopharmacological value of these peels against P. aeruginosa infections.

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PMID: 

Arch Physiol Biochem. 2019 Nov 5:1-13. Epub 2019 Nov 5. PMID: 31687854

Abstract Title: 

Assessment of antidiabetic potential ofpeel extract and its fractions in experimental animals and characterisation of its bioactive compounds by HPTLC.

Abstract: 

is a rich source of nutritional food with acclaimed therapeutic uses. Banana pulp has been reported to possess antidiabetic properties. The present study aimed to investigate antidiabetic potential ofpeels and its fractions along with diabetic complications. Animals were divided into various groups ( = 6), EMA 100, 200 and 400 mg/kg/day and various fractions 50 and 100 mg/kg/day along with vehicle administered orally to alloxan-induced diabetic rats ( = 6) for 21 days for extract and for 7 days for fractions.possess antidiabetic potential by reducing plasma glucose by utilising glucose in the periphery and production of hepatic glycogen and further reduce protein catabolism which is responsible for improvement in body weight along with reduction in diabetic complications such as dyslipidemia, peripheral neuropathy and nephropathy. Protective role ofin treatment of diabetes and its complications.

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PMID: 

Molecules. 2019 Dec 13 ;24(24). Epub 2019 Dec 13. PMID: 31847066

Abstract Title: 

NO-, IL-1β-, TNF-α-, and IL-6-Inhibiting Effects and Trypanocidal Activity of Banana () Bracts and Flowers: UPLC-HRESI-MS Detection of Phenylpropanoid Sucrose Esters.

Abstract: 

Banana inflorescences are a byproduct of banana cultivation consumed in various regions of Brazil as a non-conventional food. This byproduct represents an alternative food supply that can contribute to the resolution of nutritional problems and hunger. This product is also used in Asia as a traditional remedy for the treatment of various illnesses such as bronchitis and dysentery. However, there is a lack of chemical and pharmacological data to support its consumption as a functional food. Therefore, this work aimed to study the anti-inflammatory action ofblossom by quantifying the cytokine levels (NO, IL-1β, TNF-α, and IL-6) in peritoneal neutrophils, and to study its antiparasitic activities using the intracellular forms of,, and. This work also aimed to establish the chemical profile of the inflorescence using UPLC-ESI-MS analysis. Flowers and the crude bract extracts were partitioned in dichloromethane and-butanol to afford four fractions (FDCM, FNBU, BDCM, and BNBU). FDCM showed moderate trypanocidal activity and promising anti-inflammatory properties by inhibiting IL-1β, TNF-α, and IL-6. BDCM significantly inhibited the secretion of TNF-α, while BNBU was active against IL-6 and NO. LCMS data of these fractions revealed an unprecedented presence of arylpropanoid sucroses alongside flavonoids, triterpenes, benzofurans, stilbenes, and iridoids. The obtained results revealed that banana inflorescences could be used as an anti-inflammatory food ingredient to control inflammatory diseases.

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PMID: 

Biomed Pharmacother. 2019 Dec ;120:109439. Epub 2019 Oct 4. PMID: 31590126

Abstract Title: 

Adipose tissue as a possible therapeutic target for polyphenols: A case for Cyclopia extracts as anti-obesity nutraceuticals.

Abstract: 

Obesity is a significant contributor to increased morbidity and premature mortality due to increasing the risk of many chronic metabolic diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle modifications such as energy restriction and increased physical activity are highly effective first-line treatment strategies used in the management of obesity. However, adherence to these behavioral changes is poor, with an increased reliance on synthetic drugs, which unfortunately are plagued by adverse effects. The identification of new and safer anti-obesity agents is thus of significant interest. In recent years, plants and their phenolic constituents have attracted increased attention due to their health-promoting properties. Amongst these, Cyclopia, an endemic South African plant commonly consumed as a herbal tea (honeybush), has been shown to possess modulating properties against oxidative stress, hyperglycemia, and obesity. Likewise, several studies have reported that some of the major phenolic compounds present in Cyclopia spp. exhibit anti-obesity effects, particularly by targeting adipose tissue. These phenolic compounds belong to the xanthone, flavonoid and benzophenone classes. The aim of this review is to assess the potential of Cyclopia extracts as an anti-obesity nutraceutical as underpinned by in vitro and in vivo studies and the underlying cellular mechanisms and biological pathways regulated by their phenolic compounds.

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PMID: 

Ann N Y Acad Sci. 2020 Jan 13. Epub 2020 Jan 13. PMID: 31930541

Abstract Title: 

Betulinic acid restores imatinib sensitivity in BCR-ABL1 kinase-independent, imatinib-resistant chronic myeloid leukemia by increasing HDAC3 ubiquitination and degradation.

Abstract: 

Although imatinib (IM) has been demonstrated to be an efficient treatment in chronic myeloid leukemia (CML), some patients still experience IM resistance and disease relapse. Through in vitro studies, we observed that HDAC3 levels were elevated in BCR-ABL1 kinase-independent, IM-resistant primary cells from CML patients and in IM-resistant K562 (K562R) cells and that downregulation of HDAC3 could enhance IM efficacy in K562R cells. Furthermore, betulinic acid (BA), a lupane-type pentacyclic triterpenoid saponin isolated from birch trees, restored IM sensitivity in the BCR-ABL1 kinase-independent, IM-resistant primary cells and in K562R cells, as well as in primary CD34bone marrow cells from CML patients. We found that BA restored IM sensitivity through inhibition of HDAC3 accumulation in cells, and that this was mediated by BA-dependent ubiquitination and degradation of HDAC3. BA at low dosage significantly increased IM antitumor effects on murine xenografts bearing K562R cells and inhibited HDAC3 expression in tumor tissue. Our findings demonstrated that HDAC3 is an essential factor in BCR-ABL1 kinase-independent IM resistance, and that BA in combination with IM may be a novel treatment strategy for overcoming IM resistance in CML.

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PMID: 

Biochem Biophys Res Commun. 2020 Jan 13. Epub 2020 Jan 13. PMID: 31948750

Abstract Title: 

Suppression of HIF-1α accumulation by betulinic acid through proteasome activation in hypoxic cervical cancer.

Abstract: 

Betulinic acid (BA) exhibits various biological activities such as anti-bacterial, anti-inflammatory, anti-human papilloma virus (HPV), and anti-cancer activities. HPV infection is associated with a high risk of cervical cancer, which is the leading cause of deaths among women worldwide. Therefore, BA is an attractive therapeutic agent for treating cervical cancer. In this study, we investigated the role of BA in regulating the hypoxia-mediated response in HeLa cells and clarified the underlying mechanism of action. We found that BA inhibited the hypoxia-induced accumulation of HIF-1α without affecting HIF-1α mRNA levels and suppressed the expression of HIF target genes, including VEGF, GLUT1, and PDK1 in HeLa cells. Additionally, BA enhanced the β1, β2, and β5 activities of the proteasome, which resulted in reduced levels of ubiquitinated proteins and HIF-1α protein in HeLa cells. However, BA treatment did not affect the deubiquitinase enzyme activity in HeLa cells. These results indicate that inhibition of HIF-1α accumulation by BA is mediated by activation of the proteasome, and BA is a potential anticancer agent for the regulation of the HIF signaling pathway.

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