Sulfoxides constitute one of the most important functional groups in organic chemistry found in numerous pharmaceuticals and natural products. Sulfoxides are usually obtained from the oxidation of the corresponding sulfides. Among various oxidants, oxygen or air are considered the greenest and most sustainable reagent. Photochemistry and photocatalysis is increasingly applied in new, as well as traditional, yet demanding, reaction, like the aerobic oxidation of sulfides to sulfoxides, since photocatalysis has provided the means to access them in mild and effective ways. In this review, we will summarize the photochemical protocols that have been developed for the oxidation of sulfides to sulfoxides, employing air or oxygen as the oxidant. The aim of this review is to present: i) a historical overview, ii) the key mechanistic studies and proposed mechanisms and iii) categorize the different catalytic systems in literature.

Keywords: aerobic oxidations; green chemistry; photocatalysis; photochemistry; sulfoxides.

Keywords: COPD; chronic bronchitis; chronic obstructive pulmonary disease; comorbidities; comorbidome; emphysema; smoking.

Purpose: Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice.

Methods: We tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 h, 3 ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1-2 h or 24 h prior to initiating ozone exposure.

Results: We found that Iso given 1-2 h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23-24 h prior to ozone. In contrast, K/X/A given 1-2 h prior to ozone increased lung and systemic inflammation.

Conclusion: Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.

Keywords: Atipamezole; Inflammation; Isoflurane; Ketamine; Ozone; Serum amyloid A; Xylazine.

Growing evidence has linked long-term fine particulate matter (PM_2.5) exposure to neurological disorders. Less is known about the individual effects of PM_2.5 components. A population-based cohort study investigated the association between long-term (1-year average) exposure to PM_2.5 components and dementia incidence among the elderly population (age, ≥65 years) in the United States. We used data from the Medicare Chronic Conditions Warehouse and a high-resolution PM_2.5 components dataset of the northeastern United States (2000-2017). We identified dementia diagnoses from patients' hospital and medical insurance records and carried out Cox proportional hazards regression to investigate their association with PM_2.5 components. Among ∼2 million participants, 15.1% developed dementia. From the single-pollutant models, hazard ratios per interquartile range increase were 1.10 (95% confidence interval [CI]: 1.09-1.11) for black carbon, 1.08 (95% CI: 1.07, 1.10) for inorganic nitrate, 1.03 (95% CI: 1.02, 1.04) for organic matter, 1.13 (95% CI: 1.11, 1.15) for sulfate, 1.07 (95% CI: 1.06, 1.07) for soil particles, and 1.04 (95% CI: 1.03, 1.05) for sea salt. Increase in exposure to black carbon and sulfate per interquartile range had the strongest associations with dementia incidence. Penalized spline models indicated that dementia incidence increased linearly with elevated black carbon concentrations, whereas the incidence of dementia was only elevated significantly following sulfate concentrations above ∼2 μg/m³. Our study suggests that long-term exposure to PM_2.5 components is significantly associated with increased dementia incidence and that different components have different neurotoxicity. Reduction of PM_2.5 emissions, especially for main sources of black carbon and sulfate, may reduce the burden of dementia in the aging United States population.

Keywords: PM2.5 components; air pollution; cohort study; dementia; long-term exposure.

Celastrus paniculatus is a traditional herb belonging to the family Celastraceae and is widely used for a number of medicinal activities in the Indian Unani and Ayurvedic systems. In this study, the extensive literature search was carried out on phytochemistry, ethnobotanical uses and pharmacological activities of C. paniculatus (Willd.) in various scientific databases as well as patents. Research on phytochemical investigation has shown the presence of monoterpenes (linalool, α-terpinyl acetate, nerol acetate), sesqueterpene esters (such as malkanguniol, malkangunin, valerenal, globulol, viridiflorol, cubenol and agarofuran derivatives), diterpenoids (such as phytone, isophytol), triterpenoids (such as lupeol, pristimerin, paniculatadiol, zeylasteral, zeylasterone, β-amyrin, squalene), alkaloids (celapanin, celapanigin, celapagin, paniculatine, celastrine, maymyrsine), fatty acids, steroids (β-sitosterol, carpesterol benzoate), flavonoids (paniculatin), benzoic acid, and vitamin C in this plant. All the reported pharmacological activities of this plant could be due to the presence of these phytochemicals. This plant possesses strong antioxidant activity which includes total flavonoid content, total phenolic content, nitric oxide scavenging activity and free radical scavenging activity. This plant possesses multiple pharmacological activities including cognition-enhancing, neuroprotective, antipsychotic, anti-depressant, antibacterial, anti-arthritic, anti-malarial, analgesic, anti-inflammatory, anti-fertility, cardiovascular, locomotor, anxiolytic, wound healing activity, anti-spasmodic, hypolipidemic, anti-cancerous and iron-chelating activity with different extracts of this plant as well as various phytoconstituents present in this plant. The objective of this review article is to discuss in detail the reported ethnopharmacological uses, phytochemistry and various pharmacological activities of C. paniculatus.

Keywords: Celastraceae; Celastrus paniculatus; Jyotishmati; Malkangni; pharmacological activities; phytochemistry.

2-Amino-2-methylpropanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCP); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if personal care products containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP-containing personal care products were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP-choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of personal care products is highly unlikely to result in toxicologically-significant systemic concentrations of AMP, and thus hepatotoxicity. We concluded that dermal exposure to AMP in personal care products is not anticipated to result in an increased risk of hepatotoxicity.

Keywords: AMP; Dermal exposure; Exposure assessment; Liver steatosis; Margin of exposure; Personal care products; Risk assessment.

Background: Previously we conducted the Herpevac Trial for Women, a randomized efficacy field trial of gD-2 HSV vaccine adjuvanted with ASO4 in 8,323 women. Subjects were selected to be seronegative for HSV-1 and HSV-2. We found that vaccine was 82% protective against culture positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of ELISA antibody to gD-2.

Methods: To better understand the results of the efficacy study, post-vaccination neutralizing antibody concentrations (Neut) to either HSV- 1 and HSV- 2 from HSV infected subjects and matched uninfected controls were measured. Statistical modeling was used to determine whether these responses correlated with protection against HSV.

Results: Neut to either HSV-1 or HSV-2 was correlated with ELISA binding antibodies to gD-2. HSV-1 or HSV-2 Neut support the observation of protection by higher antibody against HSV-1 infection but the lack of protection against HSV 2 remains unexplained.

Conclusions: The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with Neut antibodies directed against the virus although the power to assess this was lower in the Neut study compared to the ELISA results due to smaller sample size.

Keywords: HSV vaccine; protective antibodies; vaccine efficacy.

Background: Strong epidemiologic evidence linking indicators of geriatric vulnerability to long-term functional outcomes after major surgery is lacking. The objective of this study was to evaluate the association between geriatric vulnerability and the burden of disability after hospital discharge for major surgery.

Methods: From a prospective longitudinal study of 754 nondisabled community-living persons, aged 70 years or older, 327 admissions for major surgery were identified from 247 participants who were discharged from the hospital from March 1997 to December 2017. The indicators of geriatric vulnerability were ascertained immediately prior to the major surgery or during the prior comprehensive assessment, which was completed every 18 months. Disability in 13 essential, instrumental and mobility activities was assessed each month.

Results: The burden of disability over the 6 months after major surgery was considerably greater for non-elective than elective surgery. In multivariable analysis, 10 factors were independently associated with disability burden: age 85 years or older, female sex, Black race or Hispanic ethnicity, neighborhood disadvantage, multimorbidity, frailty, one or more disabilities, low functional self-efficacy, smoking, and obesity. The burden of disability increased with each additional vulnerability factor, with mean values (credible intervals) increasing from 1.6 (1.4-1.9) disabilities for 0-1 vulnerability factors to 6.6 (6.0-7.2) disabilities for 7 or more vulnerability factors. The corresponding values were 1.2 (0.9-1.5) and 5.9 (5.0-6.7) disabilities for elective surgery and 2.6 (2.1-3.1) and 8.2 (7.3-9.2) disabilities for non-elective surgery.

Conclusions: The burden of disability after hospital discharge for major surgery increases progressively as the number of geriatric vulnerability factors increases. These factors can be used to identify older persons who are particularly susceptible to poor functional outcomes after major surgery, and a subset may be amenable to intervention, including frailty, low functional self-efficacy, smoking, and obesity.

Keywords: disability; longitudinal study; older persons; surgery; vulnerability.

Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant-induced lung injury. MG53 is a vital component of cell membrane repair and lung protection. Here, we show that mice with ablation of MG53 are more susceptible to NM-induced lung injury than the wild-type mice. Treatment of wild-type mice with exogenous recombinant human MG53 (rhMG53) protein ameliorates NM-induced lung injury by restoring arterial blood oxygen level, by improving dynamic lung compliance and by reducing airway resistance. Exposure of lung epithelial and endothelial cells to NM leads to intracellular oxidative stress that compromises the intrinsic cell membrane repair function of MG53. Exogenous rhMG53 protein applied to the culture medium protects lung epithelial and endothelial cells from NM-induced membrane injury and oxidative stress, and enhances survival of the cells. Additionally, we show that loss of MG53 leads to increased vulnerability of macrophages to vesicant-induced cell death. Overall, these findings support the therapeutic potential of rhMG53 to counteract vesicant-induced lung injury.

Keywords: MG53; acute lung injury; nitrogen mustard; oxidative stress.

Purpose: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood.

Methods: We scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG.

Results: Our findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric.

Conclusion: Our findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions.

Keywords: Alzheimer’s disease; Functional connectivity; Graph analysis; Mild cognitive impairment; Neural activity; PET/MR.

Adult plant stem rust resistance locus, QSrGH.cs-2AL, was identified in durum wheat Glossy Huguenot and mendelised as Sr63. Markers closely linked with Sr63 were developed. An F₃ population from a Glossy Huguenot (GH)/Bansi cross used in a previous Australian study was advanced to F₆ for molecular mapping of adult plant stem rust resistance. Maturity differences among F₆ lines confounded assessments of stem rust response. GH was crossed with a stem rust susceptible F₆ recombinant inbred line (RIL), GHB14 (M14), with similar maturity and an F_6:7 population was developed through single seed descent method. F₇ and F₈ RILs were tested along with the parents at different locations. The F₆ individual plants and both parents were genotyped using the 90 K single nucleotide polymorphism (SNP) wheat array. Stem rust resistance QTL on the long arms of chromosomes 1B (QSrGH.cs-1BL) and 2A (QSrGH.cs-2AL) were detected. QSrGH.cs-1BL and QSrGH.cs-2AL were both contributed by GH and explained 22% and 18% adult plant stem rust response variation, respectively, among GH/M14 RIL population. RILs carrying combinations of these QTL reduced more than 14% stem rust severity compared to those that possessed QSrGH.cs-1BL and QSrGH.cs-2AL individually. QSrGH.cs1BL was demonstrated to be the same as Sr58/Lr46/Yr29/Pm39 through marker genotyping. Lines lacking QSrGH.cs-1BL were used to Mendelise QSrGH.cs-2AL. Based on genomic locations of previously catalogued stem rust resistance genes and the QSrGH.cs-2AL map, it appeared to represent a new APR locus and was permanently named Sr63. SNP markers associated with Sr63 were converted to kompetetive allele-specific PCR (KASP) assays and were validated on a set of durum cultivars.

The transmembrane protease angiotensin converting enzyme 2 (ACE2) is a protective regulator within the renin angiotensin system and additionally represents the cellular receptor for SARS-CoV. The release of soluble ACE2 (sACE2) from the cell surface is hence believed to be a crucial part of its (patho)physiological functions, as both, ACE2 protease activity and SARS-CoV binding ability, are transferred from the cell membrane to body fluids. Yet, the molecular sources of sACE2 are still not completely investigated. In this study, we show different sources and prerequisites for the release of sACE2 from the cell membrane. By using inhibitors as well as CRISPR/Cas9-derived cells, we demonstrated that, in addition to the metalloprotease ADAM17, also ADAM10 is an important novel shedding protease of ACE2. Moreover, we observed that ACE2 can also be released in extracellular vesicles. The degree of either ADAM10- or ADAM17-mediated ACE2 shedding is dependent on stimulatory conditions and on the expression level of the pro-inflammatory ADAM17 regulator iRhom2. Finally, by using structural analysis and in vitro verification, we determined for the first time that the susceptibility to ADAM10- and ADAM17-mediated shedding is mediated by the collectrin-like part of ACE2. Overall, our findings give novel insights into sACE2 release by several independent molecular mechanisms.

Keywords: ADAM10; ADAM17; SARS-CoV receptor; ectodomain shedding; soluble ACE2.

Motivation: Biomarkers with prognostic ability and biological interpretability can be used to support decision-making in the survival analysis. Genes usually form functional modules to play synergistic roles, such as pathways. Predicting significant features from the functional level can effectively reduce the adverse effects of heterogeneity and obtain more reproducible and interpretable biomarkers. Personalized pathway activation inference can quantify the dysregulation of essential pathways involved in the initiation and progression of cancers, and can contribute to the development of personalized medical treatments.

Results: In this study, we propose a novel method to evaluate personalized pathway activation based on signalling entropy for survival analysis (SEPA), which is a new attempt to introduce the information-theoretic entropy in generating pathway representation for each patient. SEPA effectively integrates pathway-level information into gene expression data, converting the high-dimensional gene expression data into the low-dimensional biological pathway activation scores. SEPA shows its classification power on the prognostic pan-cancer genomic data, and the potential pathway markers identified based on SEPA have statistical significance in the discrimination of high-risk and low-risk cohorts and are likely to be associated with the initiation and progress of cancers. The results show that SEPA scores can be used as an indicator to precisely distinguish cancer patients with different clinical outcomes, and identify important pathway features with strong discriminative power and biological interpretability.

Availability: The MATLAB-package for SEPA is freely available from https://github.com/xingyili/SEPA.

Supplementary information: Supplementary data are available at Bioinformatics online.

The boreal forest biome is a major component of Earth's biosphere and climate system that is projected to shift northward due to continued climate change over the coming century. Indicators of a biome shift will likely first be evident along the climatic margins of the boreal forest and include changes in vegetation productivity, mortality, and recruitment, as well as overall vegetation greenness. However, the extent to which a biome shift is already underway remains unclear because of the local nature of most field studies, sparsity of systematic ground-based ecological monitoring, and reliance on coarse resolution satellite observations. Here, we evaluated early indicators of a boreal forest biome shift using four decades of moderate resolution (30 m) satellite observations and biogeoclimatic spatial datasets. Specifically, we quantified interannual trends in annual maximum vegetation greenness using an ensemble of vegetation indices derived from Landsat observations at 100,000 sample sites in areas without signs of recent disturbance. We found vegetation greenness increased (greened) at 38 [29, 42] % and 22 [15, 26] % of sample sites from 1985 to 2019 and 2000 to 2019, whereas vegetation greenness decreased (browned) at 13 [9, 15] % and 15 [13, 19] % of sample sites during these respective periods [95% Monte Carlo confidence intervals]. Greening was thus 3.0 [2.6, 3.5] and 1.5 [0.8, 2.0] times more common than browning and primarily occurred in cold sparsely treed areas with high soil nitrogen and moderate summer warming. Conversely, browning primarily occurred in the climatically warmest margins of both the boreal forest biome and major forest types (e.g., evergreen conifer forests), especially in densely treed areas where summers became warmer and drier. These macroecological trends reflect underlying shifts in vegetation productivity, mortality, and recruitment that are consistent with early stages of a boreal biome shift.

Keywords: Arctic Boreal Vulnerability Experiment (ABoVE); Landsat; browning; climate change; ecotone; forest productivity; greening; tree mortality; tree recruitment; warming.

Since the 1960s, rapid urbanization has caused serious deterioration in the quantity and quality of instream flows in South Korea. As demands for healthy instream ecology, landscape, and water-friendly environments have increased, the government has revised the relevant legal codes. In 2017, the environmental flow, defined as the minimum flow to conserve the health of aquatic ecosystems, has been endorsed in the Water Environment Conservation Act. However, owing to the lack of established criteria for the selection of target sites, the implementation of environmental flow is still in its early stage. This study suggests a simple flowchart to identify the preferential target sites for environmental flow estimation. First, deterioration in the health of aquatic ecosystems is identified by comparing the monitored Fish Assessment Index (FAI) with the standard suggested by the Ministry of Environment. Thereafter, the conditions of discharge and water quality of the instream flows are assessed. In the discharge analysis, linear regression is used for three flow metrics to analyze the interannual variability of discharge. Discharge deficiency is evaluated by comparing the drought flow (Q₃₅₅) and the 10% mean annual flow. The load duration curve (LDC) is used in the water quality analysis. A case study is conducted for the Bokha-cheon Stream to test the flowchart, followed by a nationwide application. From the results, more than 70 sites have been identified as target sites for the estimation of the environmental flow in the five major river basins of Korea.

Keywords: Aquatic ecosystem; Environmental flow; Load duration curve; Mean annual flow; Water quality.

Therapist factors are generally thought to be important predictors of the capacity to understand and respond to clinical material. The current study aims to identify which features of personality and clinical symptomatology predict a trainee therapist's rating of cognitive-behavioural (CB) and psychodynamic-interpersonal (PI) processes in video recordings of these therapies. 80 psychology trainees completed the MMPI-2-RF and watched two video recordings of therapy sessions showing prototypical examples of cognitive-behavioural (CB) and psychodynamic-interpersonal (PI) psychotherapy, rating the processes they could identify using the Comparative Psychotherapy Process Scale (CPPS). Trainees accurately differentiated CB from PI process while viewing the CB session, but rated the CB video higher in PI processes than the PI video itself. Bayesian regression models showed that the most consistent MMPI-2-RF scale that predicted variance in ratings was Hypomanic activation (RC9) predicting higher ratings of all psychotherapy processes in both conditions, while clinical scale factors such as Aggression (AGGR-r), and personality scale factors of Psychoticism (PSYC-r) and Neuroticism (NEGE-r) showed some notable but less consistent predictions. The variances in psychotherapy process ratings accounted for by MMPI-2-RF scales ranged from 15% to 51%. The study suggests that some clinical symptoms and personality factors do influence the rating of psychotherapy processes by psychology trainees but further studies would be required to substantiate such findings. These findings have relevance to therapist training, selection for clinical training and therapist mental health.

Although active learning methodologies promote students' creativity and motivation regarding learning objectives, traditional unidirectional teaching methods remain more common. The objective of this study was to determine nursing students' perceptions regarding the efficacy of narrative photography as a learning method, including self-perceived satisfaction. Narrative photography is an art-based technique inspired by Photovoice that promotes empathy, creativity, and reflection. A cross-sectional study was conducted using a non-probabilistic sample of 66 nursing students from a public university in Barcelona (Spain). Quantitative and qualitative data were collected anonymously using an electronic tool. Descriptive statistics and thematic analyses were used to analyze the data. Sixty valid questionnaires were returned. The respondents found narrative photography's ability to promote creativity and assist understanding of theory to be its most satisfying aspect (>95% somewhat/totally agree). Meanwhile, narrative photography's usefulness, ability to foster self-criticism, and the associated workload was the least satisfactory aspect (>55% somewhat/totally agree). Significant differences regarding satisfaction levels were found for both age and sex. Narrative photography is a helpful and satisfactory learning method, especially for promoting creativity and understanding theoretical concepts.

Keywords: Active Learning; Efficacy; Narrative Photography; Nursing Students; Teaching Innovation.

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the "3R" principle of "Refining, Reducing and Replacing" animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models. Among the animal-free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal-free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non-animal-based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal-free approaches.

Keywords: 3R; Alzheimer’s; Parkinson’s; animal research; non-animal methods; replacement.

Objective: Elevated serum levels of sialic acid (SA) have been verified in patients with various inflammatory conditions. The association between the Crohn's disease (CD) activity and serum SA has been insufficiently studied.

Materials and methods: Serum SA concentrations were determined using an enzymatic colorimetric assay method, and the correlation of SA with the Harvey-Bradshaw Index (HBI) and other inflammation activity markers was evaluated using the Spearman correlation. The predictive value of SA in estimating CD disease activity was assessed using the receiver operating characteristic.

Results: The SA levels were positively correlated with HBI and C-reactive protein (CRP) levels. The correlation of SA with the HBI was superior to that of CRP with the HBI. The area under the curve for SA was higher than that for CRP, with an optimal cutoff value of 53.14 mg/dL for active CD.

Conclusion: Serum SA correlates with the HBI score better and has better predictive value in monitoring CD disease activity than CRP or other inflammatory markers.

Keywords: Crohn’s disease; Harvey-Bradshaw Index; diagnostic marker; disease activity; inflammatory markers; sialic acid.

Objective: To study the effects of ibuprofen on androgen production, gene expression, and cell viability in rat theca-interstitial cells exposed to the proinflammatory stimuli interleukin-1β (IL-1β) and lipopolysaccharide (LPS).

Design: Animal study.

Setting: University-based research laboratory.

Patients/animals: Theca-interstitial cells were isolated from 30 day old female Sprague Dawley rats.

Interventions: Theca cells were cultured with pro-inflammatory media containing IL-1β and LPS and compared with cells cultured in control media.

Main outcome measures: Androstenedione quantification was performed on conditioned cell culture medium using liquid chromatography-mass spectrometry. Theca cell viability was assessed using PrestoBlue cell viability assay. The gene expression of Cyp17a1, Cyp11a1, and Hsd3b was analyzed using quantitative polymerase chain reaction.

Results: Both proinflammatory stimuli IL-1β and LPS increased androstenedione concentration in cell culture medium, and these effects were mitigated with ibuprofen. Both inflammatory agents in addition increased the expression of key genes involved in androgen synthesis: Cyp17a1, Cyp11a1, and Hsd3b; the addition of ibuprofen to the culture medium inhibited these effects. Theca cell viability increased with IL-1β and LPS. Ibuprofen inhibited the IL-1β-mediated increase in cell viability but did not reverse the effects of LPS.

Conclusions: In conclusion, our findings support the hypothesis that many of the alterations induced by inflammatory stimuli in theca-interstitial cells are abrogated by the addition of ibuprofen.

Keywords: Androgen excess; inflammation; polycystic ovary syndrome.