Perceptions of health professionals using the Umbiflow portable continuous wave doppler in two (2) urban hospitals in South Africa

Master of Public Health - MPHSouth Africa had a stillbirth rate of 16.4/1000 in 2019. Umbiflow is a sophisticated portable continuous wave Doppler device with bidirectional indication of blood flow velocity in the umbilical cord. Umbiflow clinical trial results have indicated that several stillbirths were avoided by screening pregnant women classed as low risk. The study aimed to describe the perceptions of health professionals on the Umbiflow screening tool. The objectives were to explore the health professionals’ perceptions on the usability, acceptability and the perceived challenges with implementation of Umbiflo

An investigation of the binding capacities of recombinant domain mutants of the human Polymeric Immunoglobulin Receptor (pIgR)

The membrane bound glycoprotein, polymeric immunoglobulin receptor (pIgR) is the primary transport molecule of the polymeric immunoglobulins, dimeric IgA and pentameric IgM, across epithelial cells. This process, known as transcytosis, is essential in order to establish immunity at mucosal surfaces. Typically, pIgR binds to the polymeric immunoglobulin at the basolateral surface of the epithelial cell, via five homologous immunoglobulin-like domains of the ectodomain. Binding is covalent to IgA and non-covalent to IgM; the IgM binding varying among species. The pIgR-bound complex is released at the apical surface of the cell after cleavage of pIgR at Arg585, thereafter referred to as secretory component (SC). SC confers protective and immunologic functions to the polymeric immunoglobulin. Free SC, i.e. not complexed with polymeric immunoglobulins, is also known to be released into mucosal secretions; and binds to pathogenic bacteria and bacterial products. It is known that domain I of the ectodomain is the primary domain in the interaction with polymeric immunoglobulins, while domain V is involved in a covalent linkage with IgA. However, little is known of domains II-IV and their role in immunoglobulin binding, particularly to IgM. This study aimed to characterize the binding of recombinant human pIgR domain mutants to polymeric IgM using immunological, biophysical and cell based techniques; thereby allowing greater insight into the contribution of each of the five domains. The unique domain structure allowed for selective amplification of single and multiple domain mutants from cloned human PIGR ectodomain cDNA. Mutants were cloned and expressed in Esherichia coli BL21 (DE3) as inclusion bodies. Recombinant mutant proteins were refolded in vitro by equilibrium gradient dialysis and purified to homogeneity. Equilibrium binding data show significant contributions to specific binding as a factor of domain presence. Binding kinetics determined by biophysical surface plasmon resonance measurements show the interplay between association and dissociation rates as defined by individual domains. In vitro competitive binding studies using the human intestinal carcinoma, HT29, known to constitutively express pIgR, show that the constructed recombinant domain mutants outcompete native pIgR. The level of competition is shown to be dependant on the domains downstream of domain I. The data also confirm the biological activity of the first in vitro refolded recombinant human SC

Photophysical behavior and photodynamic therapy activity of conjugates of zinc monocarboxyphenoxy phthalocyanine with human serum albumin and chitosan

Zincmonocarboxyphenoxy phthalocyanine (ZnMCPPc) was linked to human serum albumin (HSA) and chitosan via amide bond formation. The photophysical behavior and photodynamic therapy (PDT) activity (against human breast adenocarcinoma cell line (MCF-7 cells) of ZnMCPPc alone and its conjugates were investigated. The conjugates showed improved fluorescence, triplet and singlet oxygen quantum yields when compared to ZnMCPPc alone. The in vitro dark cytotoxicity and PDT studies were carried out at a dose of 3.6 μg/mL to 57.1 μg/mL. The in vitro dark cytotoxicity studies of ZnMCPPc showed cell viability more than 50% at 28.6 μg/mL and 57.1 μg/mL, while the conjugates showed > 50% in all their tested concentrations (3.6 to 57.1) μg/mL. Thus, conjugation of ZnMCPPc to HSA and chitosan improves its dark cytotoxicity, an important criteria for molecules meant for photodynamic therapy. Complex 1 showed the most efficacious PDT activity with cell viability more than 50% at concentration range of (14.3 to 57.1) μg/mL in comparison to the conjugates which only showed more than 50% cell viability at 28.6 μg/mL and 57.1 μg/mL for 1-HSA and 57.1 μg/mL for 1-Chitosan

Photophysicochemical properties of nanoconjugates of zinc (II) 2 (3)-mono-2-(4-oxy) phenoxy) acetic acid phthalocyanine with cysteamine capped silver and silver–gold nanoparticles

A novel asymmetrical zinc(II) 2(3)-mono-2-(4-oxy)phenoxy)acetic acid phthalocyanine (complex 1) was synthesized and subsequently linked to cysteamine capped silver (AgNPs) and silver–gold (AgAuNPs) nanoparticles (NPs) via amide bonds. The photophysicochemical properties and in vitro photodynamic therapy activity of complex 1 and its nanoconjugates were investigated. The nanoconjugates showed improved photophysical properties compared to complex 1 alone. The fluorescence, triplet and singlet quantum yields of complex 1 were found to be 20%, 48%, and 43% respectively. Complex 1 showed in vitro dark cytotoxicity, but the dark toxicity was reduced for the combination of complex 1 with AgAuNPs, this combination also gave the best photodynamic therapy activity when compared to complex 1 and its conjugate with AgNPs without AuNPs

Synthesis, characterization and photodynamic activity of Sn (iv) triarylcorroles with red-shifted Q bands

Two Sn(IV) triarylcorroles were synthesised and characterized. The absorption spectrum of a meso-thien-2-yl substituted tin(IV)corrole (1-Sn) is red shifted compared to its phenyl analogue (2-Sn) and shows no sign of aggregation in solution. 1-Sn and 2-Sn exhibited singlet oxygen quantum yields of 0.87 and 0.54 in DMF, and have a triplet lifetime of 31 and 50 μs, respectively. Time dependent cellular uptake in MCF-7 cells for 1-Sn reached a peak at 24 h, and 1-Sn was found to be more lipophilic than 2-Sn. 1-Sn showed good photo-cytotoxicity on exposure to a Thorlabs 625 nm LED with an IC50 value of 3.2 μM and remained inactive in the dark

Folic acid-modified phthalocyanine-nanozyme loaded liposomes for targeted photodynamic therapy

The hypoxic tumour microenvironment and poor spatiotemporal localization of photosensitizers are two significant obstacles that limit practical applications of photodynamic therapy. In response, a biocompatible, light-activatable liposome integrated with both a zinc phthalocyanine photodynamic component and Pt nanoparticles-decorated with MnO2 catalase-mimicking component are engineered. This multifunctional system was rationally designed using unsaturated phospholipids to achieve on-demand drug release following light irradiation. Specificity was achieved by folic acid functionalization resulting in folate-modified liposomes (FTLiposomes). We demonstrated its specific uptake by fluorescence imaging using folate receptor (FR) overexpressing HeLa and MCF-7 cells as in vitro models. This multifunctional liposome exhibits superior hypoxic anti-tumour effects and holds the potential to reduce side effects associated with untargeted therapy. Fluorescence of the constituent ZnPc and folate-receptor targeting could enable tracking and permit spatiotemporal regulation for improved cancer treatment

Step-by-step assembly and testing of a low-cost bioprinting solution for research and educational purposes

Bioprinting is a rapidly expanding technology with the ability to fabricate in vitro three-dimensional (3D) tissues in a layer-by-layer manner to ultimately produce a living tissue which physiologically resembles native in vivo tissue functionality. Unfortunately, large costs associated with commercially available bioprinters severely limit access to the technology. We investigated the potential for modifying a low-cost commercially available RepRap Prusa iteration 3 (i3) 3D printer with an open-source syringe-housed microextrusion print-head unit (universal paste extruder by Richard Horne, RichRap), that allowed for controlled deposition of cell-laden bioinks and Freeform Reversible Embedding of Suspended Hydrogels (FRESH) method-based printing.The National Research Foundation of South Africa, the South African Medical Research Council (SAMRC) and Rhodes University for funding. JRH was the recipient of an Ada & Bertie Levenstein Bursary.http://www.elsevier.com/locate/mexhj2021Immunolog

Effects of pluronic silica nanoparticles on the photophysical and photodynamic therapy behavior of triphenyl-p-phenoxy benzoic acid metalloporphyrins

5, 10, 15, Triphenyl-20-p-phenoxy benzoic acid porphyrins (P) containing Zn (ZnP), Ga (GaP), and Si (SiP) were synthesized and conjugated to pluronic-silica (PluS) nanoparticles (NPs) where the fluorescence and singlet oxygen generating behavior of the porphyrins were investigated. The highest singlet oxygen quantum yield (ΦΔ) was obtained for ZnP. When the porphyrins were conjugated to the PluS NPs, the ΦΔ was quenched and fluorescence was enhanced. The pore size of the NPs upon conjugation decreased from 18.9 nm for PluS NPs to 2.4 nm (for ZnP as an example) as determined by applying the Brunauer–Emmett–Teller method. The porphyrin complexes and their conjugates were tested for their photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. It was found that ZnP and its conjugate showed the highest PDT activity. The p > 0.05 indicated that ZnP is significantly different than GaP and SiP

Effects of Pluronic F127 micelles as delivering agents on the vitro dark toxicity and photodynamic therapy activity of carboxy and pyrene substituted porphyrins

Metal free, Zn and ClGa containing carboxyphenoxy and phenoxy groups (complexes 1) and pyrene groups (complexes 2) were synthesized and embedded into Pluronic F127 micelles (represented as F127). Dark toxicity and photodynamic therapy activities of the embedded porphyrins were successfully studied on MCF-7 breast cancer cells. Dark toxicity showed more than 80% cell viability for all complexes. It was found that 1-Zn + F127 showed better photodynamic therapy activity compared to 1-H2 + F127, and 1-ClGa + F127, corresponding to the high partition coefficient for the Zn porphyrin derivatives. The same applies to 2-Zn + F127 compared to 2-H2 + F127, 2-ClGa + F127. 1-ClGa and 1-Zn were also linked to Pluronic F127 silica nanoparticles. PDT activities for embedded 1-ClGa + F127 and 1-Zn + F127 were much higher than when linked to Pluronic silica nanoparticles (PluS NPs), showing the importance of loading of porphyrins into Pluronic F127 as a drug delivering agent rather than linking. PDT studies at the highest concentration of 60 µg/ml showed decrease in cell viability down to 15.9% for 2-Zn + F127. The Kp was determined in biphasic octanol and water system

The photophysicochemical properties and photodynamic therapy activity of In and Zn phthalocyanines when incorporated into individual or mixed Pluronic® micelles

The synthesis, photophysicochemical properties and photodynamic activity (PDT) of tetra-pyridyloxy (1,2) and benzothiazole (3, 4) substituted indium (III) (1,3) and zinc (2, 4) phthalocyanines (Pcs) and their incorporation into Pluronic® F127 and Pluronic L121/F127 mixed micelles (the latter for 3 and 4 only) are presented in this study. The InPcs exhibited higher singlet oxygen (ΦΔ) at 0.76 and 0.68 compared to the ZnPc’s at 0.47 and 0.44 in dimethyl sulfoxide. The ΦΔ values in the presence of Pluronic® F127 and in water, were 0.39 and 0.42 for InPcs and 0.23 and 0.37 for ZnPc. The ΦΔ values in the presence of Pluronic F127/L121 mixed micelles for complex 3 and 4 were 0.51 and 0.29 in water. The Kp was determined using the water and octanol system. InPcs had larger Kp values suggesting that they are more likely to be taken up by the cancer cells hence they showed better PDT activit