Role of chemokine receptors in inflammation-induced haematopoietic progenitor cell mobilisation

Background: There is a high cellular turnover in the haematopoietic system which necessitates that new cells are continuously produced to replace old and senescent ones. The haematopoietic stem cells and its progenitors meet this requirement. In adults, haematopoietic stem and progenitor cells (HSPCs) generally occupy a unique microenvironment in the bone marrow called the niche. However, recent findings have shown that approximately 0.06% of HSPCs circulate between bone marrow and periphery in steady state. Evidence shows that HSPC express cytokine receptors and pathogen recognition receptors [e.g. Toll-like receptors (TLRs)], which suggest that HSPCs may directly respond to inflammation and infection. The capacity of HSPCs to directly respond to infection is demonstrated in models of bacterial infection using LPS injection that significantly increases the number of circulating HSPCs. However, the underlying mechanism is not clearly understood. As chemokines orchestrate in vivo cellular migration, it was hypothesised that HSPC inducibly express inflammatory chemokine receptors that enable them to respond to circulating chemokines during infection and inflammation. Methods and results: Here, the impact of systemic or peripheral inflammation on HSPC of mice was investigated using LPS injection and topical imiquimod cream/TPA treatment respectively. Using haematopoietic progenitor colony-forming assays, RT-QPCR on isolated progenitors, gene-knockout mice, flow cytometric analysis and in vivo antibody-mediated neutralisation experiments, data are provided showing that HSPC inducibly express chemokine receptors in response to inflammation. Critically, the topical imiquimod inflammation model required functional chemokine receptor 2 (Ccr2) for HSPC mobilisation in contrast to both systemic LPS and topical TPA models, which were Ccr2-independent. Furthermore, dermal inflammation was necessary for imiquimod-mediated HSPC mobilization, as subcutaneously administered imiquimod did not result in significant HSPC mobilization. Conclusion: The data suggest that, in addition to the established CXCR4-CXCL12 axis that regulates homeostatic HSPC trafficking, the inflammatory chemokine-chemokine receptor axes may also be crucial in modulating HSPC functions during infection and inflammation

Banks’ Governance, Capital Structure and Performance in Ghana

The paper explores the mechanisms through which banks rely on good governance to attract more equity capital towards the improvement of their profitability. The study employed a panel data for twenty-nine commercial banks in Ghana between the years from 2003 to 2015, using the Generalized Method of Moments (GMM), Fixed Effects and Random Effects estimators. The results are robust notwithstanding the estimation method employed, that bank governance affects banks’ performance in Ghana. Larger board size improves return on the banks’ equity just as large proportion of directors with finance expertise induces bank performance. All estimates also show that equity funding has a negative and significant effect on bank performance. The paper also found evidence that good bank governance attracts equity capital which, in turn, induces greater profitability. The study recommends for managers and policymakers of banks to adopt policies that will position the banks to improve governance structure, to improve managerial expertise to drive bank performance. Admonitions to expand bank capitalisation should not be encouraged without recourse to the improvement in bank governance effectiveness

Misleading presentation of haemoglobin electrophoresis data

Haemoglobinopathies are common in sub-Saharan Africa. As such haemoglobin electrophoresis are required to inform clinical decision making. However, haemoglobin electrophoresis is an assay that detects protein at either alkaline or acidic pH. Such assays do not interrogate gene sequences but rather the product of a gene. As many posttranscriptional and post-translational modifications impact the final output of the gene (i.e. protein), presentation of such protein-based assay must accurately reflect the technique employed. It is grossly misleading and scientifically inaccurate to report cellulose acetate and/or citrate agar haemoglobin electrophoresis results as ‘haemoglobin genotype’.We propose a new paradigm in which haemoglobin electrophoresis data would be presented as ‘haemoglobin phenotype’ at a specified pH.Funding: None declaredKeywords: Electrophoresis, haemoglobinopathies, haemoglobin, cellulose acetate electrophoresis, citrate agar electrophoresi

Purified Acidic Sophorolipid Biosurfactants in Skincare Applications: An Assessment of Cytotoxic Effects in Comparison with Synthetic Surfactants Using a 3D In Vitro Human Skin Model

Acidic sophorolipids (Acidic SL), congeners of sophorolipid biosurfactants, offer a potential alternative to synthetic sodium lauryl ether sulphate (SLES) in skincare applications. However, major challenges associated with the laboratory-based investigations of the cytotoxic effects of Acidic SL have been the utilisation of impure and/or poorly characterised congeners as well as the use of monolayers of skin cells in in vitro assays. While the former limitation makes glycolipids less attractive for use in academic research and skincare applications, the latter does not provide an accurate representation of the in vivo human skin. The present study, therefore, for the first time, assessed the cytotoxic effects of 96% pure Acidic SL on a 3D in vitro skin model in comparison with SLES, with the aim of investigating a natural alternative to synthetic surfactants for potential use in skincare applications. The 3D in vitro skin model was colonised with Staphylococcus epidermidis for 12 h, and afterwards treated with either Acidic SL or SLES at 100 μg mL−1 for a further 12 h. Subsequently, the cytotoxic effects of Acidic SL in comparison with SLES were assessed using a combination of microbiology, molecular biology techniques, immunoassays, and histological analyses. It was demonstrated that Acidic SL had no deleterious effects on the viability of S. epidermidis, tissue morphology, filaggrin expression, and the production of inflammatory cytokines in comparison to SLES. These findings, in conjunction with the possibility to produce Acidic SL from cheaper renewable natural resources, demonstrate that Acidic SL could offer a potential sustainable alternative to synthetic surfactants

Characterisation of cytotoxicity and immunomodulatory effects of glycolipid biosurfactants on human keratinocytes

ABSTRACT: Skin irritation and allergic reactions associated with the use of skincare products formulated with synthetically derived surfactants such as sodium lauryl ether sulphate (SLES) have encouraged the search for naturally derived and biocompatible alternatives. Glycolipid biosurfactants such as sophorolipids (SL) and rhamnolipids (RL) offer a potential alternative to SLES. However, most studies on the bioactive properties of microbial glycolipids were determined using their mixed congeners, resulting in significant inter-study variations. This study aims to compare the effects of highly purified SL (acidic and lactonic) and RL (mono-RL and di-RL) congeners and SLES on a spontaneously transformed human keratinocyte cell line (HaCaT cells) to assess glycolipids’ safety for potential skincare applications. Preparations of acidic SL congeners were 100% pure, lactonic SL were 100% pure, mono-RL were 96% pure, and di-RL were 97% pure. Cell viability using XTT assays, cell morphological analyses, and immunoassays revealed that microbial glycolipids have differing effects on HaCaT cells dependent on chemical structure. Compared with SLES, acidic SL and mono-RL have negligible effects on cell viability, cell morphology, and production of pro-inflammatory cytokines. Furthermore, at non-inhibitory concentrations, di-RL significantly attenuated IL-8 production and CXCL8 expression while increasing IL-1RA production and IL1RN expression in lipopolysaccharide-stimulated HaCaT cells. Although further studies would be required, these results demonstrate that as potential innocuous and bioactive compounds, microbial glycolipids could provide a substitute to synthetic surfactants in skincare formulations and perform immunopharmacological roles in topical skin infections such as psoriasis. KEY POINTS: • Purified glycolipid congeners have differing effects on human keratinocytes. • Compared with SLES, acidic sophorolipids and mono-rhamnolipids have innocuous effects on keratinocytes. • Di-rhamnolipids and mono-rhamnolipids modulate cytokine production in lipopolysaccharide stimulated human keratinocytes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-022-12302-5

Epidemiology of cervical human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among a cohort of HIV-infected and uninfected Ghanaian women.

BACKGROUND: There is limited data in Ghana on the epidemiology of HPV and cervical neoplasia and their associations with HIV. This study aimed to compare among HIV-1 seropositive and HIV-seronegative Ghanaian women: (1) the prevalence, genotype distribution and risk factors associated with cervical HPV infection; and (2) the prevalence and risk factors associated with abnormal cervical cytology. METHODS: A comparative frequency-matched study was conducted in a systematic sample of women aged ≥18 years attending HIV and general outpatient clinics in Cape Coast Teaching Hospital, Ghana. Participants were interviewed and cervical samples collected for HPV genotyping (Seegene Anyplex-II HPV28) and cytological testing. RESULTS: Overall, 333 women were recruited, 163 HIV-1 seropositive and 170 HIV-seronegative women of mean age 43.8 years (SD ±9.4)) and 44.3 years (SD ±12.8), respectively. The prevalence of 14 high-risk (hr) HPV genotypes was higher among HIV-1 seropositive women (65.6% vs. 30.2%, P < 0.0001), as was proportion with multiple hr.-HPV infections (60.6% vs. 21.3%, P < 0.0001). HPV35 was the most prevalent hr.-HPV genotype in both groups (11.9% and 5.3%). The main factors associated with hr.-HPV infection were age for HIV-positive women and circumcision status of main sexual partner for both HIV-negative and positive women. Abnormal cervical cytology prevalence was higher among HIV-1 seropositive women (any SIL: 14.1% vs. 1.2%, P < 0.0001; low-grade SIL [LSIL]: 4.9% vs. 0.6%, P = 0.02; high-grade SIL: 1.8% vs. 0%, P = 0.07). Among HIV-1 seropositive women, number of pregnancies and CD4+ cell count were associated with LSIL+ cytology. There was strong association between LSIL+ abnormalities and HPV35 (aOR = 4.7, 95%CI: 1.3-17.7, P = 0.02). CONCLUSIONS: HIV-1 infected women bear significant burden of HPV infection and related disease. Prevention and screening programmes should be specifically deployed for this population in Ghana

Theoretical Modeling of the Impact of Salt Precipitation on CO2 Storage Potential in Fractured Saline Reservoirs

Deep saline reservoirs have the capacity to hold large volumes of CO2. However, apart from the high brine salinity, which poses an injectivity challenge, a high percentage of saline reservoirs are also fractured. The mechanisms of drying and salt precipitation and the resulting impact on CO2 injection are unique in fractured reservoirs. Analytical models were developed to investigate the impact of salt precipitation on CO2 injectivity and storage capacity. Two types of fractured saline reservoirs were considered: type I fractured reservoirs, where storage capacity and injectivity are contributed by only fractures, and type II fractured reservoirs, where both fractures and the adjacent rock matrix blocks contribute to CO2 storage and injectivity. We found that, depending on the initial brine salinity, salt precipitation could severely impair CO2 injectivity and reduce storage capacity. Salt precipitation had a fourfold impact on CO2 injectivity compared to storage capacity. Type I reservoirs with high irreducible brine saturation were less susceptible to salt clogging in the fractures. The results also suggest that fractures with rectangular aperture were less likely to be plugged by salt compared to elliptical fractures. Contrary to previous reports, some fractured deep saline reservoirs may not be suitable for CO2 storage. Generally, type II fractured reservoirs were found to be more suitable for CO2 storage in terms of susceptibility to salt clogging. The findings provide valuable understanding of the mechanisms and effect of drying and salt precipitation on CO2 storage potential, making a strong case for CO2 storage in naturally fractured deep saline reservoirs.publishedVersio