Social Determinants of COVID-19 Pandemic Control: Participatory Learnings From Everyday Experiences in Cape Town, South Africa.

Introduction: As countries adapted their disaster responses to the COVID-19 pandemic, South Africa responded with an alert-level risk approach based on epidemiological principles that impacted all societal levels. We explored the everyday experiences of people in Cape Town whose basic needs were met and who could report on the realities of the COVID-19 pandemic control. Gaining insight into their perspectives contributes to knowledge that can inform policies and practices for managing future public health crises.

Identification of South African Plant-Based Bioactive Compounds as Potential Inhibitors against the SARS-CoV-2 Receptor.

The expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized "safe and effective" vaccines. This study focuses on extracts of South African medicinal plants, and , to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer.

Recent advances in genome annotation and synthetic biology for the development of microbial chassis.

This article provides an overview of microbial host selection, synthetic biology, genome annotation, metabolic modeling, and computational methods for predicting gene essentiality for developing a microbial chassis. This article focuses on lactic acid bacteria (LAB) as a microbial chassis and strategies for genome annotation of the LAB genome. As a case study, Lactococcus lactis is chosen based on its well-established therapeutic applications such as probiotics and oral vaccine development.

A simplified workflow with end-point validation of real-time electrical cell-substrate impedance sensing of retinoic acid stimulated neurogenesis in human SH-SY5Y cells in vitro.

Objective: Retinoic acid (RA) is known to transition proliferating SH-SY5Y neuroblastoma cells towards functional neurons. However, the activity of RA is restricted due to its photolability where any findings from prolonged time course observations using microscopy may alter outcomes. The aim of the study was to establish a real-time, long-term (9-day) protocol for the screening of differentiation events using Electrical cell-substrate impedance sensing (ECIS).

Recent advances in genetic tools for engineering probiotic lactic acid bacteria.

Synthetic biology has grown exponentially in the last few years, with a variety of biological applications. One of the emerging applications of synthetic biology is to exploit the link between microorganisms, biologics, and human health. To exploit this link, it is critical to select effective synthetic biology tools for use in appropriate microorganisms that would address unmet needs in human health through the development of new game-changing applications and by complementing existing technological capabilities.

Reflections of volunteer counselors working remotely during the COVID-19 pandemic-Implications for policy and practice.

Purpose: We reflect on our experience of running a remote volunteer counseling service, known as the Counseling Collective, to support patients and their families during the second wave of the COVID-19 pandemic in Cape Town, South Africa, and the learning and implications for practice and policy regarding the effective utilization of volunteers during a crisis or disaster context.

Background: The Beta SARS-Co-2 variant dominated the second COVID-19 wave which gained momentum in December 2020, as public sector health teams prepared to deescalate services over the South African summer season. The ferocity with which the wave hit the city soon made it clear that volunteers would be needed to assist with counseling services as the Beta variant caused serious disease, resulting in a significant upswing in hospitalisations and deaths.

A hypoxia responsive silicon phthalocyanine containing naphthquinone axial ligands for photodynamic therapy activity.

A liposome loaded‑silicon (IV) phthalocyanine (SiPc) containing naphthoquinone axial ligands as hypoxia-responsive a prodrug-like moieties (Prodrug-SiPc), is herein reported. With the help of computational methods, this study assessed the photophysical, photochemical and electrochemical redox properties of the Prodrug-SiPc to elucidate the relationship between material structure and properties. The attachment of the axial quinoid moieties endowed the Prodrug-SiPc with Type I/II photochemical and prodrug-like properties.

Opportunity Neglect: An Aversion to Low-Probability Gains.

Seven preregistered studies ( = 2,890, adult participants) conducted in the field, in the lab, and online documented opportunity neglect: a tendency to reject opportunities with low probability of success even when they come with little or no objective cost (e.g., time, money, reputation).

Analysis of the galactomannan binding ability of β-mannosidases, BtMan2A and CmMan5A, regarding their activity and synergism with a β-mannanase.

Both β-mannanases and β-mannosidases are required for mannan-backbone degradation into mannose. In this study, two β-mannosidases of glycoside hydrolase (GH) families 2 (BtMan2A) and 5 (CmMan5A) were evaluated for their substrate specificities and galactomannan binding ability. BtMan2A preferred short -oligomers, while CmMan5A preferred longer ones; DP >2, and galactomannans.

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 MnO catalase-mimicking component are engineered. This multifunctional system was rationally designed using unsaturated phospholipids to achieve on-demand drug release following light irradiation.

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 commercially available STAT3 inhibitor 5,15-diphenylporphyrin (5,15-DPP) does not directly interact with STAT3 core residues 127-722.

Objective: Target specific small molecule inhibitors has driven signaling pathway discovery and are used as common positive controls in drug discovery screens. During a biophysical screen, using surface plasmon resonance spectroscopy, of a novel small molecule library for the Signal Transducer and Activator of Transcription 3 Src Homology 2 (STAT3-SH2) low molecular weight interactors we evaluated commercial inhibitors S3I-201 and 5,15-diphenylporphyrin (5, 15-DPP) as positive controls.

Results: Here, we show using surface plasmon resonance spectroscopy that a common STAT3-SH2 inhibitor, 5,15-diphenylporphyrin (5, 15-DPP), does not bind STAT3 core amino acid residues 127 to 722 relative to another commercially available SH2 inhibitor, S3I-201.

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment.

Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling.

Bioprinting: Prospects, considerations and challenges for application in South African clinical environments.

Bioprinting advances have revolutionised drug discovery and are set to disrupt biomedical research and medical application through the development of reproducible, fine-tuned functional 3D tissues and, eventually, whole organs. This intersectional bottom-up approach of additive manufacturing requires collaboration between tissue engineers, materials chemists, software and electrical engineers and medical practitioners for the software, hardware and wetware required by this disruptive technology. This review provides a current overview of the state of the art of bioprinting and the biomaterials/bioinks required, as well as the challenges and prospects for medical application in South Africa.

Prevalence of vitamin D deficiency and associated comorbidities among Abu Dhabi Emirates population.

Objective: The study explored the prevalence of vitamin D deficiency, its seasonal variation and associated comorbidities among the Abu Dhabi Emirati population living in urban and suburban settings.

Result: Of the 12,346 participants 36.9% were male and 63.

Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones.

A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones have been prepared and shown to exhibit promising concentration-dependent activity against human SH-SY5Y cells, Plasmodium falciparum, Mycobacterium tuberculosis and P. aeruginosa. Substituent effects on observed bioactivity have been explored; the para-fluorophenyl derivative 3d exhibited activity across the range of the bioassays employed, indicating the potential of the 2-chloro-3-[(4-arylthiazol-2-yl)amino]-1,4-naphthoquinone scaffold in the development of novel, broad spectrum therapeutics.

An acidic loop within the human soluble CD23 protein may direct the interaction between sCD23 and the αβ integrin.

CD23 is involved in a myriad of immune reactions. It is not only a receptor for IgE, but also functions in the regulation of IgE synthesis, isotype switching in B cells, and induction of the inflammatory response. These effector functions of CD23 arise through its interaction with another leukocyte-specific cell surface receptor - the β integrin subfamily.

Preparation of NIR absorbing axial substituted tin(iv) porphyrins and their photocytotoxic properties.

Sn(iv) porphyrins ([Sn(iv)TTP(3PyO)] () and [Sn(iv)TPP(3PyO)] () [tetrathienylporphyrin (TTP), tetraphenylporphyrin (TPP), and pyridyloxy (PyO)]) were prepared and characterized and their photocytotoxicity upon irradiation with 625 nm light has been studied. The presence of the 3PyO axial ligands was found to limit the aggregation and enhance the solubility of and in DMF/HO (1 : 1). The photophysical properties and photodynamic therapy (PDT) activity of the -2-thienyl and -phenyl-substituted Sn(iv) porphyrins are compared.

Photophysicochemical and photodynamic therapy properties of metallophthalocyanines linked to gold speckled silica nanoparticles.

This work reports on the linkage of 2(3),9(10),16(17),23(24) tetrakis [(benzo[d]thiazol-2-yl phenoxy) phthalocyaninato] zinc(II) (1) and indium(III) chloride (2) to gold speckled silica (GSS) nanoparticles via gold to sulphur (Au-S) and gold to nitrogen (Au-N) self-assembly to form the conjugates: 1-GSS and 2-GSS. The formed conjugates were characterized using microscopic and spectroscopic techniques, and the photophysicochemical properties and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) were studied. The conjugates afforded decrease in fluorescence quantum yields with corresponding increase in triplet and singlet oxygen quantum yields when compared to phthalocyanines alone.

Comparative detection method of early onset cytokine-induced stress in β-cells (INS-1E).

β-Cells contain a prominent endoplasmic reticulum (ER), disrupting ER homeostasis and function, activating the unfolded protein response (UPR). Currently, no direct protocols measure the UPR initiation. Current methods to measure ER stress include the quantification of nitric oxide (NO) (indirect method), Western blotting, and qRT-PCR of downstream components.

Measuring breast density: Comparing computer-automated breast density quantification with an observer-based method in a South African academic context.

Background: Dense breast tissue may not only 'mask' small, non-calcified cancers but also represents an independent risk factor for the development of breast cancer. Computer-automated breast density quantification (CABD) software tools have been developed for the calculation of volumetric breast density.

Objectives: This study sought: (1) to compare observer-based breast density scores, using the fifth edition of the Breast Imaging Reporting and Data System (BI-RADS), with the breast density scores calculated using CABD quantification software tools, (2) to determine inter-reader variability in breast density scoring between qualified radiologists, between radiologists in training (registrars) and between these two groups and (3) to determine intra-reader reliability in breast density scoring.

Photodynamic therapy activity of zinc phthalocyanine linked to folic acid and magnetic nanoparticles.

In this work, the photodynamic therapy (PDT) activities (using human carcinoma adherent MCF-7 cells) of zinc phthalocyanine derivatives: complexes 1 (Zn mono cinnamic acid phthalocyanine) and 2 (zinc mono carboxyphenoxy phthalocyanine) when covalently linked to folic acid (FA) and amine functionalized magnetic nanoparticles (AMNPs) are reported. The covalent linkage of asymmetric zinc cinnamic acid Pc (1) to FA (1-FA) through an amide bond is reported for the first time. Complex 1 is insoluble in water, but upon linkage to FA, (to form 1-FA) the molecule become water soluble, hence the UV-Vis spectrum and singlet oxygen quantum yield for 1-FA were also done in water since water solubility is essential for biological applications.

Photophysicochemical properties and photodynamic therapy activity of highly water-soluble Zn(II) phthalocyanines.

The syntheses of two zinc(II) phthalocyanines (ZnPcs) having either imidazole (ZnPc 1) or pyridiloxy (ZnPc 2) moieties as their macrocycle substituents are reported. Quaternization of the ZnPcs with methyl iodide afforded water soluble cationic phthalocyanines. The photophysical, photochemical properties and photodynamic therapy (PDT) activity of the ZnPcs were studied in solution.

Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70.

Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. Hsp70s are also implicated in the survival and pathogenicity of malaria parasites. The main agent of malaria, Plasmodium falciparum, expresses six Hsp70s.

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

Zinc monocarboxyphenoxy 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.