PMID: 

Environ Sci Technol. 2019 Oct 1 ;53(19):11420-11428. Epub 2019 Sep 16. PMID: 31453682

Abstract Title: 

Immunotoxic Potential of Bisphenol F Mediated through Lipid Signaling Pathways on Macrophages.

Abstract: 

As a bisphenol A (BPA) alternative, bisphenol F (BPF) has been detected in various products, such as paper products, personal care products, and food. More importantly, the toxicity of BPF remains underexplored. We reported an integrated method to study the immunotoxic potentials and the underlying mechanisms of BPF on cell apoptosis, macrophage polarization, reactive oxygen species generation, expression and secretion of immune-related cytokines, and reprogramming of lipid signaling. More serious to BPA, BPF induced apoptosis in macrophages. The apoptosis was induced by activating both sphingomyelin-ceramide signaling pathway and oxidative stress, which included intrinsic (bax and caspase-9) and extrinsic apoptotic pathways (tumor necrosis factor receptor 1, caspase-8, and caspase-3). BPF exposure also induced the proinflammatory phenotype of the macrophage. This alternation was shown to be closely correlated with the modulation of biosynthesis and degradation of glycerophospholipids. This study demonstrated novel evidence that BPF as a substituent of BPA induced immunotoxic effects at environmentally relevant concentrations. We also showed that the reprogramming of lipidome plays a key role in the regulation of macrophage polarization and the induction of immunotoxicity of the BPA analogue.

read more

PMID: 

Environ Int. 2019 Oct 19:105185. Epub 2019 Oct 19. PMID: 31668669

Abstract Title: 

Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven.

Abstract: 

BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.OBJECTIVES: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.METHODS: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.RESULTS: Using repeated holdout validation, IQ scores were 1.9-points (CI = -3.6, -0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.CONCLUSION: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.

read more

PMID: 

Environ Health Perspect. 2019 Oct ;127(10):107013. Epub 2019 Oct 30. PMID: 31663775

Abstract Title: 

Exposure to Bisphenol A and Bisphenol S and Incident Type 2 Diabetes: A Case-Cohort Study in the French Cohort D.E.S.I.R.

Abstract: 

BACKGROUND: The question of whether exposure to bisphenol A (BPA) contributes to the development of type 2 diabetes is still unresolved. Most epidemiological evidence on the association between BPA and diabetes is from cross-sectional studies or longitudinal studies with single urinary measurements. No prospective study has examined exposure to BPA analogs such as bisphenol S (BPS) in relation to incident type 2 diabetes.OBJECTIVES: We aimed to investigate whether exposure to BPA and BPS, assessed at up to two time points, was associated with the incidence of type 2 diabetes.METHODS: We performed a case-cohort study on 755 participants without diabetes at baseline and followed-up over 9 y as part of the French prospective cohort Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.). BPA-glucuronide (BPA-G) and BPS-glucuronide (BPS-G) were assessed in fasting spot urine samples collected during the health examinations at baseline and 3 y later. Associations with incident diabetes were examined using Prentice-weighted Cox regression models adjusted for potential confounders.RESULTS: A total of 201 incident cases of type 2 diabetes were diagnosed over the follow-up, including 30 in the subcohort. Compared with participants with the lowest average BPA exposure (below the first quartile), participants in the second, third, and fourth quartile groups of exposure had a near doubling of the risk of type 2 diabetes, with a hazard ratio2.56 (95% CI: 1.16, 5.65), 2.35 (95% CI: 1.07, 5.15), and 1.56 (95% CI: 0.68, 3.55), respectively. The detection of BPS-G in urine at one or both time points was associated with incident diabetes, with an2.81 (95% CI: 1.74, 4.53).DISCUSSION: This study shows positive associations between exposure to BPA and BPS and the incidence of type 2 diabetes, independent of traditional diabetes risk factors. Our results should be confirmed by recent, population-based observational studies in different populations and settings. Overall, these findings raise concerns about using BPS as a BPA substitute. Further research on BPA analogs is warranted. https://ift.tt/2WDRWIm.

read more

PMID: 

Chem Biol Interact. 2019 Oct 24:108866. Epub 2019 Oct 24. PMID: 31669319

Abstract Title: 

Bisphenol S triggers the malignancy of hemangioma cells via regulation of basic fibroblast growth factor.

Abstract: 

Hemangioma (IHA) is the most common benign tumor in infants caused by hyperproliferation of mesoblastic vascular tissues. Studies indicated that estrogenic signals have positive roles in its progression, while potential roles of endocrine disrupting compounds (EDCs) on its development are largely unknown. Our present study found that bisphenol S (BPS), the"safety"analog of bisphenol A (BPA), can trigger proliferation of HA cells and induce G1 to S transition of cell cycle at nanomolar concentrations. Further, BPS increased the expression of basic fibroblast growth factor (bFGF) in HA cells. Knockdown of bFGF can attenuate BPS-induced proliferation of HA cells, suggesting the essential role of bFGF in BPS-induced HA development. BPS can increase the transcription and mRNA stability of bFGF, while had no effect on its mRNA export or protein stability. Mechanistically, BPS can activate p65 to initiate bFGF transcription and decrease miR-155-5p to upregulate the mRNA stability of bFGF. Collectively, our study revealed that BPS can trigger the malignancy of HA cells via induction of cell proliferation and cell cycle transition. This is due to that BPS can increase the expression of bFGF via activation of p65 and down regulation of miR-155-5p.

read more

PMID: 

Cell Death Dis. 2019 Oct 14 ;10(10):779. Epub 2019 Oct 14. PMID: 31611561

Abstract Title: 

Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia.

Abstract: 

Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca. At lethal concentrations, CBD causes mitochondrial Caoverload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment.

read more

PMID: 

Altern Ther Health Med. 2019 Oct 1. Epub 2019 Oct 1. PMID: 31634872

Abstract Title: 

Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives.

Abstract: 

The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.

read more

PMID: 

Neurotox Res. 2019 Oct 22. Epub 2019 Oct 22. PMID: 31637586

Abstract Title: 

Cannabidiol and Cannabinoid Compounds as Potential Strategies for Treating Parkinson's Disease and L-DOPA-Induced Dyskinesia.

Abstract: 

Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient's quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure. Manipulation of the endocannabinoid system could be a promising therapy to control PD and LID symptoms. In this way, phytocannabinoids and synthetic cannabinoids, such as cannabidiol (CBD), the principal non-psychotomimetic constituent of the Cannabis sativa plant, have received considerable attention in the last decade. In this review, we present clinical and preclinical evidence suggesting CBD and other cannabinoids have therapeutic effects in PD and LID. Here, we discuss CBD pharmacology, as well as its neuroprotective effects and those of other cannabinoids. Finally, we discuss the modulation of several pro- or anti-inflammatory factors as possible mechanisms responsible for the therapeutic/neuroprotective potential of Cannabis-derived/cannabinoid synthetic compounds in motor disorders.

read more

PMID: 

Glia. 2019 Oct 24. Epub 2019 Oct 24. PMID: 31647138

Abstract Title: 

Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS/NF-κB-dependent signaling and glucose consumption.

Abstract: 

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS, 10 ng/ml) to study the anti-inflammatory potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis. Under LPS stimulation, CBD (1-10μM) potently inhibited the release of prototypical proinflammatory cytokines (TNF-α and IL-1β) and that of glutamate, a noncytokine mediator of inflammation. The effects of CBD were predominantly receptor-independent and only marginally blunted by blockade of CB2 receptors. We established that CBD inhibited a mechanism involving, sequentially, NADPH oxidase-mediated ROS production and NF-κB-dependent signaling events. In line with these observations, active concentrations of CBD demonstrated an intrinsic free-radical scavenging capacity in the cell-free DPPH assay. Of interest, CBD also prevented the rise in glucose uptake observed in microglial cells challenged with LPS, as did the inhibitor of NADPH oxidase apocynin and the inhibitor of IκB kinase-2, TPCA-1. This indicated that the capacity of CBD to prevent glucose uptake also contributed to its anti-inflammatory activity. Supporting this view, the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) mimicked the antioxidant/immunosuppressive effects of CBD. Interestingly, CBD and 2-DG, as well as apocynin and TPCA-1 caused a reduction in glucose-derived NADPH, a cofactor required for NADPH oxidase activation and ROS generation. These different observations suggest that CBD exerts its anti-inflammatory effects towards microglia through an intrinsic antioxidant effect, which is amplified through inhibition of glucose-dependent NADPH synthesis. These results also further confirm that CBD may have therapeutic utility in conditions where neuroinflammatory processes are prominent.

read more

PMID: 

J Dermatol. 2015 Mar ;42(3):296-9. Epub 2015 Jan 13. PMID: 25639454

Abstract Title: 

Acne patients frequently associated with abnormal plasma lipid profile.

Abstract: 

This study was designed to investigate the relationship between plasma lipid profile and acne. Acne patients (n = 181) and healthy volunteers (n = 130) matched in terms of both age and sex were enrolled. Plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein (LP)(a) levels were measured. TC, LDL-C and LP(a) levels in male and female patients with severe acne were significantly higher than in the healthy control group (P

read more

PMID: 

Clin Lab. 2014 ;60(7):1201-5. PMID: 25134390

Abstract Title: 

Serum lipid profile in female patients with severe acne vulgaris.

Abstract: 

BACKGROUND: Acne vulgaris is one of the most common skin conditions affecting young adults. The relationship between lipid profile or lipid ratios and acne is not widely reported.METHODS: A case control study was performed in 90 females with severe acne vulgaris. Lipid profiles were measured, lipid ratios were calculated, and results were compared with 90 age matched healthy controls.RESULTS: Total cholesterol, LDL-C, HDL-C, Apo A1, though, were significantly higher in patients as compared to healthy controls but all the levels in patients were within normal range so we calculated lipid ratios for TC/HDL, LDL/HDL, TG/HDL, Apo B/Apo A1, Atherogenic index of plasma and found that all the ratios were significantly higher as compared to controls using a t-test. The area under receiver operating characteristic curve was>0.7 for all the lipid ratios and sensitivity and specificity were calculated for all the ratios and it was highest for Apo A1/Apo B.CONCLUSIONS: We suggest using lipid ratios as a screening test in females with acne vulgaris to diagnose dyslipidemia at an early stage but further studies are required to see the effect of treating hyperlipidemia in females with severe acne vulgaris.

read more