PMID: 

Antioxidants (Basel). 2019 Dec 24 ;9(1). Epub 2019 Dec 24. PMID: 31878141

Abstract Title: 

A Combination ofExtracts and Gold Complex Favors Apoptosis of Caco-2 Cells by Increasing Oxidative Stress and Mitochondrial Dysfunction.

Abstract: 

Given the alarming increase in colorectal cancer (CRC) worldwide, novel therapies are urgently needed. Plant-derived extracts have gained considerable interest in the last years due to their strong anticancer effect mediated by their unique bioactive compounds. Specifically, rosehips fromhave been successfully tested against several cancer models, including colon cancer. Moreover, gold derivatives are a promising alternative to the current platinum-based drugs commonly used in CRC chemotherapy due to their lack of affinity for DNA. Herein we have investigated the antitumor potential of a drug combination made of acidic polyphenols extracted fromand the gold complex (Au(C≡C-2-NCH) (PTA)) in Caco-2 cell line as a model of CRC. The combination triggered strong apoptosis mediated by a blockage of the autophagic flux, which might be a consequence of a reactive oxygen species (ROS) increase and mitochondrial dysfunctionality. Our results suggest that the clinical application of plant polyphenols might enhance the anticancer effect of metallodrugs and reduce drug exposure time and therefore its side effects.

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PMID: 

Antioxidants (Basel). 2019 Dec 25 ;9(1). Epub 2019 Dec 25. PMID: 31881765

Abstract Title: 

Antioxidative and Anti-Inflammatory Properties of Cannabidiol.

Abstract: 

Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids ofL. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.

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PMID: 

Antioxidants (Basel). 2019 Dec 26 ;9(1). Epub 2019 Dec 26. PMID: 31888113

Abstract Title: 

Endoplasmic Reticulum Stress-Induced Resistance to Doxorubicin Is Reversed by Mulberry Leaf Polyphenol Extract in Hepatocellular Carcinoma through Inhibition of COX-2.

Abstract: 

Mulberry (L.) leaves are used in Chinese medicine to treat metabolic disorders. Mulberry leaf polyphenol extracts (MLPE) have recently been shown to exhibit anticancer properties. Endoplasmic reticulum (ER) stress represents a pivotal obstacle in solid tumors, resulting in the antiapoptosis of tumor cells and drug resistance. In this study, pretreatment with the ER stress inducer tunicamycin (TM) attenuated the percentage of apoptosis induced by doxorubicin (DOX). Cotreatment with tunicamycin and MLPE reversed apoptosis induced by DOX. Simultaneously, induction of ER stress with tunicamycin resulted in an increased expression of Cyclooxygenase 2 (COX-2) and Glucose-regulated protein (GRP78) concomitant with the activation of p38 MAPK/PI3K/Akt in HepG2 cells. Furthermore, the suppression of ER stress with celecoxib or p38 MAPK inhibitor successfully recovered DOX-induced apoptosis. Consistent with the inhibition of COX-2 or p38 MAPK, copretreatment with TM and MLPE drastically recovered cytotoxicity and caspase-3 activation in the presence of DOX. These results reveal that MLPE reduces ER stress-induced resistance to DOX in hepatocellular carcinoma (HCC) cells through downregulation of COX-2- or p38 MAPK-mediated PI3K/Akt pathway.

PMID: 

Antioxidants (Basel). 2019 Dec 27 ;9(1). Epub 2019 Dec 27. PMID: 31892217

Abstract Title: 

Chemopreventive Effect ofβ-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis.

Abstract: 

The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities ofβ-cryptoxanthin derived from mandarin oranges (Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established thatβ-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the ICvalue of 4.5 and 3.7µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclearcondensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin.

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PMID: 

Antioxidants (Basel). 2019 Dec 16 ;8(12). Epub 2019 Dec 16. PMID: 31888243

Abstract Title: 

Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats.

Abstract: 

Evidence suggests that oxidative stress plays a major role in the development of metabolic syndrome. This study aims to investigate whetherα-lipoic acid (LA), a potent antioxidant, could exert beneficial outcomes in Zucker diabetic fatty (ZDF) rats. Male 6-week-old ZDF rats and their lean counterparts (ZL) were fed for six weeks with a standard diet or a chow diet supplemented with LA (1 g/kg feed). At 12 weeks of age, ZDF rats exhibited an increase in systolic blood pressure, epididymal fat weight per body weight, hyperglycemia, hyperinsulinemia, insulin resistance (HOMA index), adipocyte hypertrophy and a rise in basal superoxide anion (O•) production in gastrocnemius muscle and a downregulation of epididymal uncoupled protein-1 (UCP-1) protein staining. Treatment with LA prevented the development of hypertension, the rise in whole body weight and O•production in gastrocnemius muscle, but failed to affect insulin resistance, hyperglycemia and hyperinsulinemia in ZDF rats. LA treatment resulted in a noticeable increase of pancreatic weight and a further adipocyte hypertrophy, along with a decrease in epididymal fat weight per body weight ratio associated with an upregulation of epididymal UCP-1 protein staining in ZDF rats. These findings suggest that LA was efficacious in preventing the development of hypertension, which could be related to its antioxidant properties. The anti-visceral obesity effect of LA appears to be mediated by its antioxidant properties and the induction of UCP-1 protein at the adipose tissue level in ZDF rats. Disorders of glucose metabolism appear, however, to be mediated by other unrelated mechanisms in this model of metabolic syndrome.

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PMID: 

Antioxidants (Basel). 2019 Sep 6 ;8(9). Epub 2019 Sep 6. PMID: 31500121

Abstract Title: 

Can Plant Phenolic Compounds Protect the Skin from Airborne Particulate Matter?

Abstract: 

The skin is directly exposed to the polluted atmospheric environment, and skin diseases, such as atopic dermatitis and acne vulgaris, can be induced or exacerbated by airborne particulate matter (PM). PM can also promote premature skin aging with its accompanying functional and morphological changes. PM-induced skin diseases and premature skin aging are largely mediated by reactive oxygen species (ROS), and the harmful effects of PM may be ameliorated by safe and effective natural antioxidants. Experimental studies have shown that the extracts and phenolic compounds derived from many plants, such as cocoa, green tea, grape, pomegranate, and some marine algae, have antioxidant and anti-inflammatory effects on PM-exposed cells. The phenolic compounds can decrease the levels of ROS in cells and/or enhance cellular antioxidant capacity and, thereby, can attenuate PM-induced oxidative damage to nucleic acids, proteins, and lipids. They also lower the levels of cytokines, chemokines, cell adhesion molecules, prostaglandins, and matrix metalloproteinases implicated in cellular inflammatory responses to PM. Although there is still much research to be done, current studies in this field suggest that plant-derived phenolic compounds may have a protective effect on skin exposed to high levels of air pollution.

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PMID: 

Toxicol Lett. 2019 Nov ;316:27-34. Epub 2019 Sep 9. PMID: 31513887

Abstract Title: 

Acceleratory effects of ambient fine particulate matter on the development and progression of atherosclerosis in apolipoprotein E knockout mice by down-regulating CD4CD25Foxp3regulatory T cells.

Abstract: 

OBJECTIVE: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4CD25Foxp3regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4CD25Foxp3Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4CD25Foxp3Tregs population and atherosclerotic development in ApoEmice exposed to PM2.5.METHODS: We employed a real-world system to subject 40 ApoEmice to ambient inhalation of PM2.5 (PM2.5 group, n = 20) or filtered air (FA group, n = 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4CD25Foxp3Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively.RESULTS: The daily average concentration of PM2.5 was 57.4 ± 25.6 μg/m. Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-α, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-β, CD4CD25Foxp3Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group.CONCLUSION: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoEmice, which is related to CD4CD25Foxp3Tregs down-regulation, as well as lipid deposition and systemic inflammation.

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PMID: 

Sci Total Environ. 2020 Jan 10 ;699:134390. Epub 2019 Sep 10. PMID: 31525546

Abstract Title: 

Ambient air pollution exposure and gestational diabetes mellitus in Guangzhou, China: A prospective cohort study.

Abstract: 

BACKGROUND: Evidence concerning the effect of ambient air pollution exposure on gestational diabetes mellitus (GDM) is limited. No published studies have examined maternal weekly air pollution exposure and GDM, and the possible effect modification by folic acid supplementation has not been assessed.OBJECTIVES: To evaluate the association between air pollution exposure and GDM at trimester and weekly levels, and to explore the potential effect modification by folic acid supplementation.METHODS: A total of 5421 pregnant women were recruited during 2011-2014 in Guangzhou, China. Daily PM, PM, SOand NOlevels were collected from 10 monitoring stations. Individual's exposure during pregnancy was estimated using inverse-distance weighting approach. Binary logistic regression was used to examine the trimester-specific association between air pollution exposure and GDM. Distributed lag models (DLMs) were applied to estimate maternal weekly air pollution exposure and GDM. Stratified analyses by folic acid supplementation and interaction test were performed.RESULTS: The GDM incidence was 11.69%. An interquartile range (IQR) increase in first trimester SOwas associated with increased GDM risk in the single pollutant model, the adjusted odds ratio (aOR) and 95% confidence interval (CI) was 1.22 (1.02-1.47). In DLMs, an IQR increase in SOduring 4th to 10th gestational weeks was associated with increased GDM risk, with the strongest effect in the 7th gestational week. When stratified by maternal folic acid supplementation, first trimester exposure to SOwas associated with increased GDM risk among women taking folic acid supplements (aOR = 1.25, 95% CI: 1.03-1.53) and P value for interaction was 0.13. No significant effects were observed for PM, PMand NO.CONCLUSION: First trimester exposure to SOwas associated with increased GDM risk, especially during the 4th to 10th gestational weeks. The effect might be stronger among women taking folic acid supplements.

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PMID: 

Mediators Inflamm. 2019 ;2019:8613523. Epub 2019 Aug 21. PMID: 31530996

Abstract Title: 

Study on the Mechanism of Curcumin Regulating Lung Injury Induced by Outdoor Fine Particulate Matter (PM2.5).

Abstract: 

Background: Epidemiological studies have shown that exposure to PM induces oxidative stress, leading to a variety of health problems. In particular, PM2.5 contains a lot of substances harmful to the human body and penetrates into the lungs to induce lung injury. At the same time, there is increasing evidence that oxidative stress also affects the severity of lung injury. However, there is still no good way to reduce or eliminate these hazards. In the future, more experimental research is needed to further confirm the mechanisms of these hazards and formulate effective preventive measures and treatment plans for their hazard mechanisms. Curcumin has been reported to reduce oxidative stress and inflammatory damage and protect organs.Objective: To investigate whether curcumin can play a protective role against PM2.5-induced oxidative stress and inflammatory damage by inducing expression of the HO-1/CO/P38 MAPK pathway.Methods: In this experiment, PM2.5 was dropped into the trachea to establish a lung injury model in mice. 28 SPF-grade male Kunming mice were randomly divided into 4 groups: normal control group, saline control group, PM2.5 treatment group, and curcumin intervention group. Albumin (ALB), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were measured in alveolar lavage fluid (BALF) to assess lung tissue damage. Colorimetric detection of oxidative stress indicators such as MDA, GSH-PX, T-AOC, and CAT in the lung tissue was performed. The levels of IL-6 and TNF-in the lung tissue were determined by ELISA. Histopathological examination was used for the assessment of alveolar epithelial damage. The protein expression of the HO-1/P38 MAPK pathway in the lung tissue was determined by Western blot and immunohistochemistry. Endogenous CO was detected by spectrophotometry. The results showed that the expression of the HO-1/CO/P38 MAPK protein in the lung tissue was significantly increased in the curcumin intervention group compared with the PM2.5 treatment group, and it was statistically significant (0.05).Conclusion: We found that PM2.5 can cause lung damage through oxidative stress and inflammatory responses. Oxidative stress and inflammatory responses increase the expression of HO-1/CO/P38 MAPK. The intervention of curcumin can further increase the expression of HO-1/CO/P38 MAPK.

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PMID: 

Environ Res. 2019 Nov ;178:108734. Epub 2019 Sep 7. PMID: 31539824

Abstract Title: 

Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children.

Abstract: 

OBJECTIVE: Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems.METHODS: Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PMexposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV.RESULTS: Prenatal PMlevels ranged from 11.8 to 39.5 μg/mduring the third trimester of pregnancy. An interquartile range increase in PMlevel (7 μg/m) was significantly linked to a decrease in the body CC volume (mm) (β = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mmdecrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons.CONCLUSIONS: Prenatal exposure to PMmay be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.

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