Biology subjects

Bell, J. D.

Publications and source records attributed to Bell, J. D..

4 recordsLinked to original sources

bioRxiv2023

Near infrared-light treatment alters mitochondrial homeostasis to induce senescence in breast cancer cells

The application of near infrared (NIR)-light to living systems has been suggested as a potential method to enhance tissue repair, decrease inflammation, and possibly mitigate cancer therapy-associated side effects. In this study, we examined the effect of exposing three cell lines: breast cancer (MCF7), non-cancer breast cells (MCF10A), and lung fibroblasts (IMR-90), to 734 nm NIR-light for 20 minutes per day for six days, and measuring changes in cellular senescence. Positive senescent populations were induced using doxorubicin. Flow cytometry was used to assess relative levels of senescence together with mitochondria-related variables. Exposure to NIR-light significantly increased the level of senescence in MCF7 cells (13.5%; P<0.01), with no observable effects on MCF10A or IMR-90 cell lines. NIR-induced senescence was associated with significant changes in mitochondria homeostasis, including raised ROS level (36.0%; P<0.05) and mitochondrial membrane potential (14.9%; P<0.05), with no changes in mitochondrial Ca2+. These results suggest that NIR-light exposure can significantly arrest the proliferation of breast cancer cells via inducing senescence, while leaving non-cancerous cell lines unaffected.

cell biology↗

bioRxiv2019

Levonorgestrel modulates innate immune activation in human endocervical epithelium and monocytes during Chlamydia trachomatis infection

ProblemOur group has previously shown that baboons with a levonorgestrel-releasing intrauterine system (LNG-IUS) have delayed clearance of Chlamydia trachomatis (Ct). Based on this result, we hypothesized that LNG results in changes to development of the immune response by epithelial and resident innate immune cells. Method of StudyUsing the end1 endocervical cell line or the THP.1 monocyte-like cell line, cells were exposed to increasing levels of progesterone (P4) or a dose of LNG representative of LNG in reproductive tract tissues of women with an LNG-IUS. Ct was used at an MOI of 1 and supernatants were collected for ELISA at 48 hours post-infection. Select nuclear receptors were inhibited to determine which receptor contributed to LNG-mediated immunosuppression. ResultsCervical epithelial cells infected with Ct expressed IL-1{beta} when treated with vehicle control. P4 further increased IL-1{beta} expression during Ct infection, while LNG decreased IL-1{beta} expression. Treatment with the androgen receptor blocker ailanthone prevented LNG-mediated immunosuppression. ConclusionsLNG in the presence of increasing P4 suppresses IL-1{beta} production in response to Ct infection in vitro. This appears to be mediated at least in part by the androgen receptor. This has implications for women with LNG-IUS at high risk for sexually transmitted infections.

immunology↗

bioRxiv2019

Effects of the copper IUD on composition of the vaginal microbiota in the olive baboon

ObjectivesAssess the impact of transcervical insertion, use, and removal of copper intrauterine devices (Cu-IUD) on baboon physiology (e.g. weight, menstruation) and vaginal microbiota.\n\nStudy designVaginal swabs were taken before insertion (pre-IUD), during IUD use (IUD), and after removal (post-IUD) and microbiota assessed by 16S rRNA-encoding gene sequence analysis.\n\nResultsNo animals showed physical changes or discomfort during pre-IUD, IUD, or post-IUD phases. There were no changes to the microbiome associated with insertion or use of Cu-IUD over 16 weeks, although removal resulted in perturbation to community structure.\n\nConclusionsBaboons tolerate Cu-IUD insertion with minimal device-associated changes to their vaginal microbiome throughout use and have no significant changes to their physiology or menstrual cycle during any phase.\n\nImplicationsA baboon model of Cu-IUD may allow investigations into the intersection of Cu-IUDs, reproductive tract disorders and pathogens that would not be possible in human studies.

microbiology↗

bioRxiv2018

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Abstract/SummaryO_ST_ABSBackground and aimsC_ST_ABSUnderstanding the aetiology, clinical presentation and prognosis of type 2 diabetes (T2D) and optimizing its treatment might be facilitated by biomarkers that help predict a persons susceptibility to the risk factors that cause diabetes or its complications, or response to treatment. The IMI DIRECT (Diabetes Research on Patient Stratification) Study is a European Union (EU) Innovative Medicines Initiative (IMI) project that seeks to test these hypotheses in two recently established epidemiological cohorts. Here, we describe the characteristics of these cohorts at baseline and at the first main follow-up examination (18-months).\n\nMaterials and methodsFrom a sampling-frame of 24,682 European-ancestry adults in whom detailed health information was available, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm and enrolled into a prospective cohort study (n=2127) undertaken at four study centres across Europe (Cohort 1: prediabetes). We also recruited people from clinical registries with recently diagnosed T2D (n=789) into a second cohort study (Cohort 2: diabetes). The two cohorts were studied in parallel with matched protocols. Endogenous insulin secretion and insulin sensitivity were modelled from frequently sampled 75g oral glucose tolerance (OGTT) in Cohort 1 and with mixed-meal tolerance tests (MMTT) in Cohort 2. Additional metabolic biochemistry was determined using blood samples taken when fasted and during the tolerance tests. Body composition was assessed using MRI and lifestyle measures through self-report and objective methods.\n\nResultsUsing ADA-2011 glycaemic categories, 33% (n=693) of Cohort 1 (prediabetes) had normal glucose regulation (NGR), and 67% (n=1419) had impaired glucose regulation (IGR). 76% of the cohort was male, age=62(6.2) years; BMI=27.9(4.0) kg/m2; fasting glucose=5.7(0.6) mmol/l; 2-hr glucose=5.9(1.6) mmol/l [mean(SD)]. At follow-up, 18.6(1.4) months after baseline, fasting glucose=5.8(0.6) mmol/l; 2-hr OGTT glucose=6.1(1.7) mmol/l [mean(SD)]. In Cohort 2 (diabetes): 65% (n=508) were lifestyle treated (LS) and 35% (n=271) were lifestyle + metformin treated (LS+MET). 58% of the cohort was male, age=62(8.1) years; BMI=30.5(5.0) kg/m2; fasting glucose=7.2(1.4)mmol/l; 2-hr glucose=8.6(2.8) mmol/l [mean(SD)]. At follow-up, 18.2(0.6) months after baseline, fasting glucose=7.8(1.8) mmol/l; 2-hr MMTT glucose=9.5(3.3) mmol/l [mean(SD)].\n\nConclusionThe epidemiological IMI DIRECT cohorts are the most intensely characterised prospective studies of glycaemic deterioration to date. Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the IMI DIRECT consortium.\n\nAbbreviations

epidemiology↗