Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived ...primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid’s pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (h TERT ) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of h TERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for β-galactosidase revealed a significantly lower number of β-gal–positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of h TERT -mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.
Keloid scars are described as benign fibro‐proliferative dermal outgrowths that commonly occur in pigmented skin post cutaneous injury, and continue to grow beyond the boundary of the original wound ...margin. There is a lack of thorough understanding of keloid pathogenesis and thus keloid therapeutic options remain ill‐defined. In view of the poor response to current therapy and high recurrence rates, there is an unmet need in improving our knowledge and therefore in identifying targeted and effective treatment strategies in management of keloids. Keloid research however, is hampered by a lack of relevant animal models as keloids do not spontaneously occur in animals and are unique to human skin. Therefore, developing novel animal models and nonanimal models for functional evaluation of keloid cells and tissue for better understanding their pathobiology and response to putative candidate therapies are essential. Here, we present the key concepts and relevant emerging research on two‐dimensional and three‐dimensional cell and tissue models for functional testing of keloid scars. We will describe in detail current models including in vitro mono‐ and co‐cultures, multi‐cellular spheroids (organoids) and organotyopic cultures, ex vivo whole skin keloid tissue organ culture models as well as in vivo human patient models. Finally, we discuss the role played by time as the fourth dimension in a novel model that involves sequential temporal biopsies of human patients with keloids (a so called 4D in vivo human model). The use of these unique models will no doubt prove pivotal in identification of new drug targets as well as biomarkers, in functional testing of emerging novel therapeutics, and in enhancing our understanding of keloid disease biology.
The number of university students coming from rural areas has significantly increased in South Africa in the last two decades. While this is a positive sign of inclusive social growth and ...development, the fact that 70% of South African universities are still located in urban areas creates challenges for a number of these students. This is also compounded by the fact that most rural schools in South Africa offer sub-optimal preparation for post-school activities. As such, the first barrier for most of these students is negotiating various levels of access to higher education (HE), using forms of social and cultural capital that may be incommensurate with urban-based HE institutions. Using an in-depth review of literature on the subject of rural education, transition to higher education, student success and reflections on the professional experience of the authors in student support services in higher education. This study argues that since most South African universities are “urban enclaves”, students from rural areas take time to adapt and accumulate relevant socio-cultural capital to enable them to thrive and succeed. The transition of students from rural schools to urban-based universities is a socio-cultural as much as it is an epistemological mobility. As such, this “troubled transition” of rural students can be ameliorated through a trans-sectoral or transdisciplinary transitional intervention to simultaneously enable epistemological access and create commensurate socio-cultural capital. However, previous interventions on student transition have been generic and lacked the nuanced intersectional analysis of rurality on student access and success. Transdisciplinary contribution: The study proposes a trans-sectoral or transdisciplinary transitional space in which education institutions (basic and HE) collaborate with government and non-state partners to ensure sufficient and effective transition, especially for rural school learners.
The what, why and how of curly hair: a review Cloete, Elsabe; Khumalo, Nonhlanhla P; Ngoepe, Malebogo N
Proceedings - Royal Society. Mathematical, physical and engineering sciences,
11/2019, Letnik:
475, Številka:
2231
Journal Article
Recenzirano
Odprti dostop
An attempt to understand and explain a peculiarity that was observed for curly fibres during experimentation revealed disparate literature reporting on several key issues. The phenotypical nature of ...curly fibres is only accurately understood within the larger scope of hair fibres, which are highly complex biological structures. A brief literature search produced thousands of research items. Besides the large amount of information on the topic, there was also great variability in research focus. From our review, it appeared that the complexity of hair biology, combined with the variety of research subtopics, often results in uncertainty when relating different aspects of investigation. During the literature investigation, we systematically categorized elements of curly hair research into three basic topics: essentially asking why fibres curl, what the curly fibre looks like and how the curly fibre behaves. These categories were subsequently formalized into a curvature fibre model that is composed of successive but distinctive tiers comprising the elements in curly hair research. The purpose of this paper is twofold: namely to present (i) a literature review that explores the different aspects of curly human scalp hair and (ii) the curvature fibre model as a systemized approach to investigating curly hair.
Understanding Curly Hair Mechanics: Fiber Strength Cloete, Elsabe; Khumalo, Nonhlanhla P.; Ngoepe, Malebogo N.
Journal of investigative dermatology,
January 2020, 2020-01-00, 20200101, Letnik:
140, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The relationship between the geometric and mechanical profiles of hair fibers has been studied, with special focus on curly samples. Incidental observations pointed to a significantly different ...viscoelastic character with varying curliness. Further investigations confirmed initial observations, showing an initial distinct toe region behavior for curly fibers on the stress-strain plot, which is absent for straight fibers. This behavior suggested a difference in the viscoelastic nature of the curly fiber that is linked to mechanical energy stored in the fiber. Results also suggest that the strength of hair depends on two main components, and further pointed out that de facto methods of tensile testing may erode curly fiber strength during preparation. The main outcome of this study is that the tensile strength (σT) of hair fibers is composed of two (rather than one main) components, namely the toe region (σt) and the elastic region (σε), so that: σT=σt+σε. For noncurly fibers, the greatest part of fiber strength is derived from σε, while σt ≈ 0. For curly fibers, σt (i.e., springiness) adds significantly to the overall strength, even though σε remains the major contributor. Although these results require validation in larger studies, they are significant in the current understanding of curly hair. Also, they may represent a fundamental shift from the current understanding of tensile testing of human hair in general.
Interventions for bullous pemphigoid Kirtschig, Gudula; Middleton, Philippa; Bennett, Cathy ...
Cochrane database of systematic reviews,
10/2010
10
Journal Article
Recenzirano
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Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005.
To assess treatments ...for bullous pemphigoid.
In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers.
Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid.
At least two authors evaluated the studies for the inclusion criteria, and extracted data independently.
We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12).
Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.
Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions ...post-cutaneous injury, remain benign yet behave locally aggressive and expansive. To date, there is limited understanding, and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim here was to identify putative-causative candidates in KD, by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analyses to demonstrate that NF-kappa-Beta-p65 (RELA) from the cytosolic fraction and Calpain-2 (CAPN2) from the whole cell lysate were significantly up-regulated in KD and associated with alterations in relevant key signalling pathways including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry, demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, to our knowledge previously unreported, subcellular fractionation and metaproteogenomic analyses have identified two novel biomarkers of relevance to keloid diagnostics and therapeutics.
Congenital poikiloderma is characterized by a combination of mottled pigmentation, telangiectasia, and epidermal atrophy in the first few months of life. We have previously described a South African ...European-descent family affected by a rare autosomal-dominant form of hereditary fibrosing poikiloderma accompanied by tendon contracture, myopathy, and pulmonary fibrosis. Here, we report the identification of causative mutations in FAM111B by whole-exome sequencing. In total, three FAM111B missense mutations were identified in five kindreds of different ethnic backgrounds. The mutation segregated with the disease in one large pedigree, and mutations were de novo in two other pedigrees. All three mutations were absent from public databases and were not observed on Sanger sequencing of 388 ethnically matched control subjects. The three single-nucleotide mutations code for amino acid changes that are clustered within a putative trypsin-like cysteine/serine peptidase domain of FAM111B. These findings provide evidence of the involvement of FAM111B in congenital poikiloderma and multisystem fibrosis.
Background Brazilian keratin treatment (BKT) and similar straightening products fix and retain a straight shape even when the hair is wet. Unacceptably high concentrations of formaldehyde have been ...reported in such products. Objective We sought to measure the formaldehyde concentration in all BKT brands marketed in South Africa in 2012. Methods We quantified formaldehyde by high-performance liquid chromatography with ultraviolet light detection after derivatization with dinitrophenylhydrazine. All components of 7 identified commercial brands were each tested 3 times. Results The maximum safe concentration of formaldehyde set by the US Cosmetic Ingredient Review Expert Panel is less than 0.2%. Of the 7 commercial BKT brands, 6 had formaldehyde levels that ranged from 0.96% to 1.4%, ie, 5 times higher than the recommended level; these included 5 brands labeled formaldehyde-free. Limitations The study is limited by not including all internationally available BKT products. Conclusions Formaldehyde concentrations in BKT products may exceed recommended levels and serve as a health hazard. Industry monitoring is needed to improve compliance and protection of hairdressers and consumers.
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