Exploring Anti-Breast Cancer Effects of Live Pediococcus acidilactici and Its Cell-Free Supernatant Isolated from Human Breast Milk.

Current breast cancer treatment options are limited by drug resistance and adverse side effects, which calls for the need for alternatives or complementary remedies. Probiotic bacteria isolated from human breast milk have been shown to possess proapoptotic and anti-inflammatory properties against breast mastitis in breastfeeding mothers and are being studied as possible anticancer regimens. Thus, this study aimed at exploring the effect of lactic acid bacteria isolated from human breast milk on MDA-MB 231 breast cancer cells. A total of twenty-two bacteria were isolated from four human breast milk samples. The isolates were characterized and identified using biochemical tests and Sanger sequencing, respectively. For in vitro experiments, we used isolated P. acidilactici to treat MDA-MB-231 cells, and an MTT assay was used to detect proliferation. RT-qPCR and wound healing assays were performed to determine the effect of the isolated P. acidilactici on breast cancer cytokine expression and migration. Exposure of MDA-MB 231 breast cancer cells to live P. acidilactici and its cell-free supernatant (CFS) for 24 h resulted in a reduction in cancer cell viability. Also, the expression of the cytokines IL-6, IL-8, and IL-10 in the breast cancer cells increased following exposure to P. acidilactici and its CFS for 24 and 72 h. Additionally, the levels of the SLUG gene remained unchanged while the TWIST1 gene was upregulated following exposure of the cancer cells to bacteria, indicating that P. acidilactici may promote epithelial-mesenchymal transition in breast cancer. Finally, the CFS significantly inhibited cancer cell mobility. These findings serve as a foundation to further investigate the usefulness of P. acidilactici as a potential therapeutic agent in breast cancer therapy.

Measurement of polarization observables T, P, and H in π0 and η photoproduction off quasi-free nucleons.

The target asymmetry T, recoil asymmetry P, and beam-target double polarization observable H were determined in exclusive π0 and η photoproduction off quasi-free protons and, for the first time, off quasi-free neutrons. The experiment was performed at the electron stretcher accelerator ELSA in Bonn, Germany, with the Crystal Barrel/TAPS detector setup, using a linearly polarized photon beam and a transversely polarized deuterated butanol target. Effects from the Fermi motion of the nucleons within deuterium were removed by a full kinematic reconstruction of the final state invariant mass. A comparison of the data obtained on the proton and on the neutron provides new insight into the isospin structure of the electromagnetic excitation of the nucleon. Earlier measurements of polarization observables in the γp→π0p and γp→ηp reactions are confirmed. The data obtained on the neutron are of particular relevance for clarifying the origin of the narrow structure in the ηn system at W=1.68GeV. A comparison with recent partial wave analyses favors the interpretation of this structure as arising from interference of the S11(1535) and S11(1650) resonances within the S11-partial wave.

Types of dairy foods and risk of fragility fracture in the prospective Nurses' Health Study cohort.

BACKGROUND: Fragility fractures present enormous health challenges for women. Dairy products provide many bone-beneficial nutrients, such as calcium and vitamin D. Individual dairy foods may exert different effects on bone health. OBJECTIVES: The aim of this study was to investigate the associations between total dairy, yogurt, milk, and cheese and fragility fracture risk among females in the prospective Nurses' Health Study (NHS) conducted in the United States. METHODS: In the current analysis, 103,003 females with mean age of 48 y were followed from 1980-2004. Proportional hazards models were used to estimate risk of first fracture (of the wrist, hip, or vertebrae) by intakes of dairy foods (total dairy, milk, yogurt, or cheese) obtained from a food frequency questionnaire. Fractures that were caused by high-trauma events were not included. We relied on self-reported data for wrist and hip fractures whereas for vertebral fractures, medical records were used to confirm cases. RESULTS: A total of 5495 incident fracture cases were documented during follow-up. After controlling for relevant confounding variables, consumption of ≥2 servings/d of total dairy (compared with <1 serving/d) was associated with lower fracture risk (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.61, 0.89). More than 2 servings of milk per day (compared with <1 serving/d) were associated with a lower fracture risk (HR: 0.85; 95% CI: 0.77, 0.94). Intakes of calcium, vitamin D, and protein from nondairy sources did not modify the effects of total dairy or milk on fracture risk. There was no association between yogurt intake and fracture risk. Intake of cheese (≥1 servings/d compared with <1 serving/wk) was weakly associated with lower fracture risk (HR: 0.89; 95% CI: 0.79, 0.99). CONCLUSIONS: Higher total dairy, milk, and cheese intakes are associated with lower risks of fracture in females in the NHS.

Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

BACKGROUND: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. OBJECTIVES: This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort. METHODS: The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. RESULTS: In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. CONCLUSION: Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

Dairy Food Intakes, Postpartum Weight Retention, and Risk of Obesity.

Excessive postpartum weight retention puts women at risk for health problems. This study aimed to investigate the effects of dairy foods on weight retention and risk of obesity in postpartum women in the Nurses' Health Study II. Weight was reported every 2 years. We identified the pre-pregnancy and postpartum exams that were approximately 2 years before and after the birth year. Dairy consumption was averaged during these 4 years. Linear models were used to assess postpartum weight retention. Multivariable models were used to estimate risk of obesity. Women with higher yogurt (≥2 servings/week vs. <1 serving/month) intakes had 0.61 pounds less postpartum weight retention. Consuming ≥ 5 cheese servings/week was associated with 0.63 pounds less weight retention than the lowest intake. Among sedentary women, only yogurt intake was associated with lower risk of postpartum obesity (RR: 0.84; 95% CI: 0.71−1.00), though of borderline statistical significance. Among women with less healthy diets, yogurt consumption was also associated with lower postpartum obesity risk (RR: 0.70; 95% CI: 0.57−0.85). In sum, higher yogurt and cheese intakes were associated with less postpartum weight retention and among higher risk women (sedentary or lower diet quality) greater yogurt intake was associated with lower risks of postpartum obesity.

The Current State of Parkinsonism in West Africa: A Systematic Review.

Parkinsonism is one of the most common neurodegenerative diseases among the elderly. Africa is experiencing an increasing burden of age-related conditions including parkinsonism. However, there is not enough data on the prevalence, symptoms, and management of the disorder in West African patients. This systematic review examines the current state of parkinsonism in West Africa by discussing its epidemiology, symptomatology, and treatment. We searched PubMed, BioMed Central, and AJOL databases from January 2000 to December 2020 for studies on parkinsonism conducted in West African countries. We included 32 studies in this review: 23 from Nigeria, 5 from Ghana, and 1 each from Benin, Mali, Niger, and Senegal. Out of the 32 reviewed studies, 11 focused on the prevalence of parkinsonism, 4 examined the genetics of Parkinson's disease (PD), and 17 described the symptomatology and therapy of parkinsonism. The prevalence of parkinsonism in West Africa ranges from 6.0% to 8.3% of neurologic admissions/consultations. The estimated crude prevalence of PD in West Africa varies from 15 to 572 per 100,000 people. Thus far, no pathogenic genetic variants have been associated with PD in the region. Levodopa is frequently used singly or in combination with other medications to manage parkinsonian symptoms, which is consistent with reports from other African regions. Most of the reviewed studies focused only on PD, limiting assessment of other forms of parkinsonism. Almost all the prevalence studies were hospital-based and monocentric, making it impossible to accurately estimate the true prevalence of parkinsonism in West Africa. Larger community-based prevalence studies are recommended to enable accurate quantification of disease burden. Future genetic investigations should consider a wider array of gene mutations associated with parkinsonism. Moreover, public health surveillance strategies should be established to monitor the epidemiology of the disorder.

What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?

We hypothesize that basal hyperinsulinemia is synergistically mediated by an interplay between increased oxidative stress and excess lipid in the form of reactive oxygen species (ROS) and long-chain acyl-CoA esters (LC-CoA). In addition, ROS production may increase in response to inflammatory cytokines and certain exogenous environmental toxins that mislead ß-cells into perceiving nutrient excess when none exists. Thus, basal hyperinsulinemia is envisioned as an adaptation to sustained real or perceived nutrient excess that only manifests as a disease when the excess demand can no longer be met by an overworked ß-cell. In this article we will present a testable hypothetical mechanism to explain the role of lipids and ROS in basal hyperinsulinemia and how they differ from glucose-stimulated insulin secretion (GSIS). The model centers on redox regulation, via ROS, and S-acylation-mediated trafficking via LC-CoA. These pathways are well established in neural systems but not ß-cells. During GSIS, these signals rise and fall in an oscillatory pattern, together with the other well-established signals derived from glucose metabolism; however, their precise roles have not been defined. We propose that failure to either increase or decrease ROS or LC-CoA appropriately will disturb ß-cell function.

Measurement of the helicity asymmetry E for the reaction γ p → π 0 p : The CBELSA/TAPS Collaboration.

A measurement of the double-polarization observable E for the reaction γ p → π 0 p is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C 4 H 9 OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from E γ = 600 to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.

The Redox Communication Network as a Regulator of Metabolism.

Key tissues are dysfunctional in obesity, diabetes, cardiovascular disease, fatty liver and other metabolic diseases. Focus has centered on individual organs as though each was isolated. Attention has been paid to insulin resistance as the key relevant pathosis, particularly insulin receptor signaling. However, many tissues play important roles in synergistically regulating metabolic homeostasis and should be considered part of a network. Our approach identifies redox as an acute regulator of the greater metabolic network. Redox reactions involve the transfer of electrons between two molecules and in this work refer to commonly shared molecules, reflective of energy state, that can readily lose electrons to increase or gain electrons to decrease the oxidation state of molecules including NAD(P), NAD(P)H, and thiols. Metabolism alters such redox molecules to impact metabolic function in many tissues, thus, responding to anabolic and catabolic stimuli appropriately and synergistically. It is also important to consider environmental factors that have arisen or increased in recent decades as putative modifiers of redox and reactive oxygen species (ROS) and thus metabolic state. ROS are highly reactive, controlled by the thiol redox state and influence the function of thousands of proteins. Lactate (L) and pyruvate (P) in cells are present in a ratio of about 10 reflective of the cytosolic NADH to NAD ratio. Equilibrium is maintained in cells because lactate dehydrogenase is highly expressed and near equilibrium. The major source of circulating lactate and pyruvate is muscle, although other tissues also contribute. Acetoacetate (A) is produced primarily by liver mitochondria where ß-hydroxybutyrate dehydrogenase is highly expressed, and maintains a ratio of ß-hydroxybutyrate (ß) to A of about 2, reflective of the mitochondrial NADH to NAD ratio. All four metabolites as well as the thiols, cysteine and glutathione, are transported into and out of cells, due to high expression of relevant transporters. Our model supports regulation of all collaborating metabolic organs through changes in circulating redox metabolites, regardless of whether change was initiated exogenously or by a single organ. Validation of these predictions suggests novel ways to understand function by monitoring and impacting redox state.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Social networks for health communication in rural Uganda: A mixed-method analysis of Dekabusa Trading Centre, Luwero County.

To reach the most vulnerable individuals in under-resourced countries, health communication interventions increasingly move towards the community level. However, little is known about how health information spreads through local social networks. This paper maps the health information network of a rural trading centre in Uganda. As part of a five-year ethnographic study of sustainable community health resources, ego networks were obtained for 231 village residents in March 2014. Using both ethnographic and social network data, we analyze how the village social network is structured, and how this structure may influence the transmission of health information. Results show a network with low average proximity, with a small number of individuals, notably key administrative officials, much closer connected to many other community members than average. However, because of social partitioning in the village network, a number of people are outside the social clusters in which the top influencers are located.

Influence of orthopedic examination on lameness scores and interobserver and intraobserver agreement in dogs with naturally occurring elbow osteoarthritis.

OBJECTIVE: To determine the influence of orthopedic examination on numerical rating score (NRS) and visual analog score (VAS) when scoring lameness in dogs with elbow osteoarthritis (OA) and to evaluate interobserver and intraobserver agreement in NRS and VAS on the basis of video-graphic gait analysis. DESIGN: Prospective blinded study. ANIMALS: Eighteen client-owned dogs with radiographically confirmed elbow OA. METHODS: Videos were obtained for all dogs at a walk and at a trot both prior to and immediately after orthopedic examination. All videos were randomly sequenced. Six observers, unaware of the timing of the video, independently assigned both NRS and VAS twice, with at least a 2-week interval. Scores were evaluated with mixed analysis of variance, and the agreement among observers was accessed by intraclass correlation coefficient (ICC). RESULTS: No difference was detected between NRS and VAS at walk or at trot before and after orthopedic examination. Numeric rating score and VAS at walk were lower than those at trot before an orthopedic examination by scores of 0.17 (P = .0018) and 3.54 (P = .0019), respectively. The ICC for both scores for all observers was >0.9. CONCLUSION: An orthopedic examination did not exacerbate the NRS and the VAS for dogs with elbow OA. Interobserver and intraobserver agreement was high for both lameness scores. CLINICAL SIGNIFICANCE: Lameness may be scored after gait evaluation in dogs with elbow OA irrespective of the timing of a comprehensive orthopedic examination.

Nutritional status of Ugandan school-children: The effect of age imprecision.

OBJECTIVES: To analyze the nutritional status of Ugandan school-children in a cross-sectional and longitudinal perspective, considering the effect of age imprecision. MATERIALS AND METHODS: Anthropometric measurements of 831 school-children (381 males and 450 females) were analyzed. A subsample of 246 children was measured in July 2014 and 2015. Stunting (based on height-for-age Z-scores), underweight (weight-for-age), and thinness (body mass index-for-age) prevalence were calculated. Three different ages were used: declared (from schools registers), attributed (based on multiple information sources), and bootstrap (from 10,000 replicates). Significant differences among malnutrition prevalence calculated with different ages and in different groups were assessed by means of bootstrap analysis. Longitudinal analysis was conducted using a paired t test. RESULTS: The mean prevalence of malnutrition calculated with declared, attributed, or bootstrap ages were very similar: stunting (11.9-12.7); underweight (5.4-5.9); thinness (3.3-3.7); and obesity (0.7). Undernutrition was more prevalent among older children, while obesity was mostly associated with young age. Obesity was equally distributed among sexes, while undernutrition was more prevalent among females of up to 10 years of age and males above 10 years. The longitudinal analysis indicated a reduction in underweight and thinness, and an increase in stunting, especially among older children. DISCUSSION: Age imprecision did not significantly affect malnutrition estimates. Despite the decline in the prevalence of thinness and underweight observed over a 1-year period, undernutrition persists, with an observed rise in stunting. On the other hand, obesity is starting to appear. Public health efforts are required to eliminate stunting and address the emerging burden of obesity.

Instituting Sustainable Geriatric Care in Africa: The Roles of Sociocultural Constructs.

The demographic shift in Africa is seeing more people make it to old age (60 years or over), a state associated with an increased risk of acquiring communicable and non-communicable diseases, and demand for specialised health care. With many African health systems still struggling with infectious diseases, inadequate funding, poor infrastructure and lack of skilled human resource for health, how best can they provide quality, sustainable geriatric care services to their ageing population? This commentary highlights "Africa's social-cultural structure" as an opportunity health policy makers could tap into, to design patient-centred, sustainable, inexpensive, and socially acceptable geriatric interventions.

Elamipretide Promotes Mitophagosome Formation and Prevents Its Reduction Induced by Nutrient Excess in INS1 ß-cells.

Elamipretide is a tetrapeptide that restores defects in mitochondrial function, binds to cardiolipin, and is being tested in clinical trials for mitochondria-related diseases. However, whether elamipretide modulates mitochondrial quality control and dynamics, processes essential to preserve mitochondrial function, is unclear. Thus, we tested the effects of elamipretide on mitochondrial morphology, mitophagosome formation, and their early disruption induced by excess nutrients in INS1 ß-cells. Elamipretide treatment was sufficient to increase engulfment of mitochondria into autophagosomes in control INS1 ß-cells, without inducing widespread changes in mitochondrial morphology or membrane potential. In an early pathogenic context mimicked by short-term exposure to nutrient excess, elamipretide treatment prevented both mitochondrial fragmentation and defects in the engulfment of mitochondria into autophagosomes. On the other hand, elamipretide did not prevent lysosomal defects induced by nutrient excess. Accordingly, elamipretide treatment did not entail benefits on pathogenic p62 and LC3II accumulation or on insulin secretory function. In conclusion, our data show that elamipretide selectively stimulates the engulfment of mitochondria into autophagosomes and prevents its defects induced by nutrient excess. Thus, we propose that improved selectivity of mitochondrial quality control processes might contribute to the benefits stemming from elamipretide treatments in other disease models.

BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment.

Obesity and its associated pathology Type 2 diabetes are two chronic metabolic and inflammatory diseases that promote breast cancer progression, metastasis, and poor outcomes. Emerging critical opinion considers unresolved inflammation and abnormal metabolism separately from obesity; settings where they do not co-occur can inform disease mechanism. In breast cancer, the tumor microenvironment is often infiltrated with T effector and T regulatory cells programmed by metabolic signaling. The pathways by which tumor cells evade immune surveillance, immune therapies, and take advantage of antitumor immunity are poorly understood, but likely depend on metabolic inflammation in the microenvironment. Immune functions are abnormal in metabolic disease, and lessons learned from preclinical studies in lean and metabolically normal environments may not translate to patients with obesity and metabolic disease. This problem is made more urgent by the rising incidence of breast cancer among women who are not obese but who have metabolic disease and associated inflammation, a phenotype common in Asia. The somatic BET proteins, comprising BRD2, BRD3, and BRD4, are new critical regulators of metabolism, coactivate transcription of genes that encode proinflammatory cytokines in immune cell subsets infiltrating the microenvironment, and could be important targets in breast cancer immunotherapy. These transcriptional coregulators are well known to regulate tumor cell progression, but only recently identified as critical for metabolism, metastasis, and expression of immune checkpoint molecules. We consider interrelationships among metabolism, inflammation, and breast cancer aggressiveness relevant to the emerging threat of breast cancer among women with metabolic disease, but without obesity.

Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells.

Triggers of the autoimmune response that leads to type 1 diabetes (T1D) remain poorly understood. A possibility is that parallel changes in both T cells and target cells provoke autoimmune attack. We previously documented greater Ca2+ transients in fibroblasts from T1D subjects than non-T1D after exposure to fatty acids (FA) and tumor necrosis factor α (TNFα). These data indicate that metabolic and signal transduction defects present in T1D can be elicited ex vivo in isolated cells. Changes that precede T1D, including inflammation, may activate atypical responses in people that are genetically predisposed to T1D. To identify such cellular differences in T1D, we quantified a panel of metabolic responses in fibroblasts and peripheral blood cells (PBMCs) from age-matched T1D and non-T1D subjects, as models for non-immune and immune cells, respectively. Fibroblasts from T1D subjects accumulated more lipid, had higher LC-CoA levels and converted more FA to CO2, with less mitochondrial proton leak in response to oleate alone or with TNFα, using the latter as a model of inflammation. T1D-PBMCs contained and also accumulated more lipid following FA exposure. In addition, they formed more peroxidized lipid than controls following FA exposure. We conclude that both immune and non-immune cells in T1D subjects differ from controls in terms of responses to FA and TNFα. Our results suggest a differential sensitivity to inflammatory insults and FA that may precede and contribute to T1D by priming both immune cells and their targets for autoimmune reactions.

Linking communities to formal health care providers through village health teams in rural Uganda: lessons from linking social capital.

BACKGROUND: Community-based programmes, particularly community health workers (CHWs), have been portrayed as a cost-effective alternative to the shortage of health workers in low-income countries. Usually, literature emphasises how easily CHWs link and connect communities to formal health care services. There is little evidence in Uganda to support or dispute such claims. Drawing from linking social capital framework, this paper examines the claim that village health teams (VHTs), as an example of CHWs, link and connect communities with formal health care services. METHODS: Data were collected through ethnographic fieldwork undertaken as part of a larger research program in Luwero District, Uganda, between 2012 and 2014. The main methods of data collection were participant observation in events organised by VHTs. In addition, a total of 91 in-depth interviews and 42 focus group discussions (FGD) were conducted with adult community members as part of the larger project. After preliminary analysis of the data, we conducted an additional six in-depth interviews and three FGD with VHTs and four FGD with community members on the role of VHTs. Key informant interviews were conducted with local government staff, health workers, local leaders, and NGO staff with health programs in Luwero. Thematic analysis was used during data analysis. RESULTS: The ability of VHTs to link communities with formal health care was affected by the stakeholders' perception of their roles. Community members perceive VHTs as working for and under instructions of "others", which makes them powerless in the formal health care system. One of the challenges associated with VHTs' linking roles is support from the government and formal health care providers. Formal health care providers perceived VHTs as interested in special recognition for their services yet they are not "experts". For some health workers, the introduction of VHTs is seen as a ploy by the government to control people and hide its inability to provide health services. Having received training and initial support from an NGO, VHTs suffered transition failure from NGO to the formal public health care structure. As a result, VHTs are entangled in power relations that affect their role of linking community members with formal health care services. We also found that factors such as lack of money for treatment, poor transport networks, the attitudes of health workers and the existence of multiple health care systems, all factors that hinder access to formal health care, cannot be addressed by the VHTs. CONCLUSIONS: As linking social capital framework shows, for VHTs to effectively act as links between the community and formal health care and harness the resources that exist in institutions beyond the community, it is important to take into account the power relationships embedded in vertical relationships and forge a partnership between public health providers and the communities they serve. This will ensure strengthened partnerships and the improved capacity of local people to leverage resources embedded in vertical power networks.

Structural Characterization and Ligand/Inhibitor Identification Provide Functional Insights into the Mycobacterium tuberculosis Cytochrome P450 CYP126A1.

The Mycobacterium tuberculosis H37Rv genome encodes 20 cytochromes P450, including P450s crucial to infection and bacterial viability. Many M. tuberculosis P450s remain uncharacterized, suggesting that their further analysis may provide new insights into M. tuberculosis metabolic processes and new targets for drug discovery. CYP126A1 is representative of a P450 family widely distributed in mycobacteria and other bacteria. Here we explore the biochemical and structural properties of CYP126A1, including its interactions with new chemical ligands. A survey of azole antifungal drugs showed that CYP126A1 is inhibited strongly by azoles containing an imidazole ring but not by those tested containing a triazole ring. To further explore the molecular preferences of CYP126A1 and search for probes of enzyme function, we conducted a high throughput screen. Compounds containing three or more ring structures dominated the screening hits, including nitroaromatic compounds that induce substrate-like shifts in the heme spectrum of CYP126A1. Spectroelectrochemical measurements revealed a 155-mV increase in heme iron potential when bound to one of the newly identified nitroaromatic drugs. CYP126A1 dimers were observed in crystal structures of ligand-free CYP126A1 and for CYP126A1 bound to compounds discovered in the screen. However, ketoconazole binds in an orientation that disrupts the BC-loop regions at the P450 dimer interface and results in a CYP126A1 monomeric crystal form. Structural data also reveal that nitroaromatic ligands "moonlight" as substrates by displacing the CYP126A1 distal water but inhibit enzyme activity. The relatively polar active site of CYP126A1 distinguishes it from its most closely related sterol-binding P450s in M. tuberculosis, suggesting that further investigations will reveal its diverse substrate selectivity.