Human C1q Induces Apoptosis in an Ovarian Cancer Cell Line via Tumor Necrosis Factor

Copyright: © 2016 Kaur, Sultan, Murugaiah, Pathan, Alhamlan, Karteris and Kishore. Human C1q is the first recognition subcomponent of the complement classical pathway that plays a vital role in the clearance of immune complexes, pathogens and apoptotic cells. C1q also has a homeostatic role involving immune and non-immune cells; these functions not necessarily involve complement activation. Recently, C1q has been shown to be expressed locally in the microenvironment of a range of human malignant tumours, where it can promote cancer cell adhesion, migration and proliferation, without involving complement activation. C1q has been shown to be present in the ascitic fluid formed during ovarian cancers. In this study, we have examined the effects of human C1q and its globular domain on an ovarian cancer cell line, SKOV3. We show that C1q and the recombinant globular modules induce apoptosis in SKOV3 cells in a dose-and time-dependent manner. C1q expression was not detectable in the SKOV3 cells. Exogenous treatment with C1q and globular heads at the concentration of 10μg/ml induced apoptosis in approximately 55% cells, as revealed by immunofluorescence microscopy and FACS. The qPCR and caspase analysis suggested that C1q and globular head modules activated TNF-α and upregulation of Fas. The genes of mTOR, RICTOR and RAPTOR survival pathways, which are often over-expressed in majority of the cancers, were significantly downregulated within few hours of the treatment of C1q and globular head modules. In conclusion, C1q, via its globular domain, induced apoptosis in an ovarian cancer cell line, SKOV3 via TNF-α induced apoptosis pathway involving upregulation of Bax and Fas. This study highlights a potentially protective role of C1q in certain cancers

Syncytiotrophoblast Extracellular Vesicles from Late-Onset Preeclampsia Placentae suppress Pro-Inflammatory immune response in THP-1 Macrophages

© 2021 Awoyemi, Motta-Mejia, Zhang, Kouser, White, Kandzija, Alhamlan, Cribbs, Tannetta, Mazey, Redman, Kishore and Vatish. Syncytiotrophoblast derived Extracellular Vesicles (STBEV) from normal pregnancy (NP) have previously been shown to interact with circulating monocytes and B cells, and induce pro-inflammatory cytokine release. Early-onset preeclampsia (EOPE) is associated with an exacerbated inflammatory response, yet there is little data regarding late-onset PE (LOPE) and immune function. Here, using a macrophage/monocyte cell line THP-1, we investigated the inflammatory potential of STBEV, comprising medium/large-STBEV (>200nm) and small-STBEV (<200nm), isolated from LOPE (n=6) and normal (NP) (n=6) placentae via dual-lobe ex-vivo placental perfusion and differential centrifugation. THP-1 cells bound and internalised STBEV isolated from NP and LOPE placentae, as revealed by flow cytometry, confocal microscopy and ELISA. STBEV-treated THP-1 cells were examined for cytokine gene expression by RT-qPCR and the cell culture media examined for secreted cytokines/chemokines. As has been previously reported, NP medium/large-STBEV significantly upregulated the transcriptional expression of TNF-α, IL-10, IL-6, IL-12, IL-8 and TGF-β compared to PE medium/large-STBEV, however, there was no significant difference in the small STBEV population between the two groups though in general, NP small STBEVs slightly upregulated the same cytokines. In contrast, LOPE STBEV (medium and large) did not induce pro-inflammatory responses by differentiated THP-1 macrophages. This decreased effect of LOPE STBEV was echoed in cytokine/chemokine release. Our results appear to suggest that STBEV from LOPE placentae do not have a major immune-modulatory effect on macrophages. In contrast, NP STBEV caused THP-1 cells to release pro-inflammatory cytokines. Thus, syncytiotrophoblast extracellular vesicles from LOPE dampen immune functions of THP-1 macrophages, suggesting an alternative mechanism leading to the pro-inflammatory environment observed in LOPE

Surfactant Protein D as a Potential Biomarker and Therapeutic Target in Ovarian Cancer

Copyright © 2019 Kumar, Murugaiah, Sotiriadis, Kaur, Jeyaneethi, Sturniolo, Alhamlan, Chatterjee, Hall, Kishore and Karteris. Surfactant protein D (SP-D) is an important innate immune molecule that is involved in clearing pathogens and regulating inflammation at pulmonary as well as extra-pulmonary sites. Recent studies have established the role of SP-D as an innate immune surveillance molecule against lung and pancreatic cancer, but little is known about its involvement in signaling pathways it can potentially activate in ovarian cancer. We focused our study on ovarian cancer by performing bioinformatics analysis (Oncomine) of datasets and survival analysis (Kaplan-Meier plotter), followed by immunohistochemistry using ovarian cancer tissue microarrays. SP-D mRNA was found to be expressed widely in different types of ovarian cancer irrespective of stage or grade. These in silico data were further validated by immunohistochemistry of clinical tissues. High transcriptional levels of SP-D were associated with unfavorable prognosis (overall and progression-free survival). We also detected SP-D protein in Circulating Tumor Cells of three ovarian cancer patients, suggesting that SP-D can also be used as a potential biomarker. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis in pancreatic cancer cells via Fas-mediated pathway. In this study, we report that treatment of SKOV3 cells (an ovarian cancer cell line) with rfhSP-D led to a decrease in cell motility and cell proliferation. This was followed by an inhibition of the mTOR pathway activity, increase in caspase 3 cleavage, and induction of pro-apoptotic genes Fas and TNF-α. These data, suggesting a likely protective role of rfhSP-D against ovarian cancer, together with the observation that the ovarian cancer microenvironment overexperesses SP-D leading to poor prognosis, seems to suggest that the tumor microenvironment components manipulate the protective effect of SP-D in vivo.GRAC

Outcome of SARS-CoV-2 variant breakthrough infection in fully immunized solid organ transplant recipients

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.SARS-CoV-2 vaccination in solid organ transplant recipients is associated with suboptimal immune response and risk for breakthrough infection. It is not known whether they are at risk of severe post-vaccine breakthrough infections in the presence of SARSCoV-2 variant of concern. We describe a case series of four fully vaccinated solid organ transplant recipients who developed SARS-CoV-2 variants of concern breakthrough infections. Three patients received BNT162b2 mRNA (Pfizer-BioNTech) and one patient received ChAdOx1 (AZD12220) COVID-19 vaccines. The patients were infected with SARS-CoV-2 variants circulating in Saudi Arabia. Two patients were infected with Alpha variant and had severe pneumonia requiring intensive care admission and ventilatory support and subsequently died. The other two patients recovered; one patient was infected with Beta variant required low supplemental oxygen via nasal flow and the other patient was infected with Delta variant and required high supplemental oxygen nasal flow. Younger patients had a better outcome than older patients. Future large studies are required to confirm our observations and to compare the different vaccine efficacy among solid organ transplants in the era of SARS-CoV-2 variants of concern

Sociodemographic characteristics and sexual behavior as risk factors for human papillomavirus infection in Saudi Arabia

This article seeks to determine the prevalence and the sociodemographic characteristics and sexual behavior risk factors for human papillomavirus (HPV) infection in a hospital-based cohort of women in Saudi Arabia

De-isolation of vaccinated COVID-19 health care workers using rapid antigen detection test

Background: COVID-19 de-isolation guidelines of health care workers (HCW) were formulated based on evidence describing the duration of infectious viral shedding of the wild SARS-CoV-2 virus. During the periods of COVID-19 vaccination and variants, a test-based approach was recommended to end isolation of HCW, based on emerging data describing the viral kinetics of COVID-19 variants. While Rapid antigen detection tests (RADT) are increasingly used in the diagnosis of COVID-19, their use is limited in de-isolation. Methods: We described the use of RADT in the de-isolation of COVID-19 vaccinated HCW with mild infection who were asymptomatic on day 7 post diagnosis in a single center retrospective cohort study during the Omicron surge. Results: Of the 480 HCWs, 173 (36%) had positive RADT. The positivity rate of RADT was not different in HCW who received two doses versus three doses of vaccine (34.4% versus 40.3%, p = 0.239). Conclusions: A symptom based, test-based approach using RADT is a useful tool in the de-isolation of HCW, with mild disease, in the era of Omicron. Further studies are required to evaluate the role of RADT in de-isolation of patients with severe COVID-19 disease

Active viral shedding in a vaccinated hospitalized patient infected with the delta variant (B.1.617.2) of SARS-CoV-2 and challenges of de-isolation

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.In the era of SARS-CoV-2 variants and COVID-19 vaccination, the duration of infectious viral shedding and isolation in post vaccine breakthrough infections is challenging and depends on disease severity. The current study described a case of SARS-CoV-2 Delta variant pneumonia requiring hospitalization. The patient received two doses of BNT162b2 COVID-19 vaccines, and he had positive SARS-CoV-2 viral cultures 12 days post symptom onset. The time between the second dose of vaccine and the breakthrough infection was 6 months. While immunosuppression is a known risk factor for prolonged infectious viral shedding, age and time between vaccination and breakthrough infection are important risk factors that warrant further studies