PMID: 

Cancer Control. 2019 Jan-Dec;26(1):1073274819871326. PMID: 31452400

Abstract Title: 

Association of Opioid Use in the Week Before Death Among Patients With Advanced Lung Cancer Having Sepsis.

Abstract: 

Opioid use can induce immunosuppression; however, it is unclear whether opioid use increases infections in patients with advanced cancers. This study assessed the association between opioid use in the week before death and mortality among patients with advanced lung cancer having sepsis. Data on opioid usage in the week before death, general information, and clinical information of the patients were collected retrospectively. The primary outcome was the association between opioid use in the week before death and mortality after sepsis. The study included 980 patients who died of advanced lung cancer between January 2003 and June 2017 (sepsis related: 413, unrelated to sepsis: 567). The average morphine equivalent daily dose in the final week was higher in the sepsis group (313.5± 510.5 mg) than in the nonsepsis group (125.2 ± 246.9 mg,

read more

PMID: 

Pharmacology. 2019 Sep 6:1-11. Epub 2019 Sep 6. PMID: 31494660

Abstract Title: 

Morphine Promotes the Angiogenesis of Postoperative Recurrent Tumors and Metastasis of Dormant Breast Cancer Cells.

Abstract: 

BACKGROUND: Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells.OBJECTIVES: We aim to investigate the influence of opioids on recurrence and metastasis of breast cancer in nude mice.METHODS: Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco's Modified Eagle's Medium, (ii) morphine (10μmol/mL), (iii) morphine plus naloxone (10 + 10 μmol/mL), and (iv) naloxone (10 μmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting.RESULTS: Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p

read more

PMID: 

Ann N Y Acad Sci. 2019 Sep 8. Epub 2019 Sep 8. PMID: 31495936

Abstract Title: 

Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA-derived circular RNA.

Abstract: 

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types, with a high annual incidence. Although chemotherapy contributes to suppressing OSCC tumorigenesis, the available treatments result in poor prognosis because of local recurrence and regional lymph node metastasis. Thus, it is necessary to discover novel and safe drugs with greater effectiveness and fewer side effects. Fucoidan is a component of the cell wall of brown seaweed that has been shown to produce a wide range of biological activities. The present study aimed to investigate the effectiveness of fucoidan in treating OSCC. In in vitro studies, we found that fucoidan inhibited OSCC growth and suppressed migration and invasion of OSCC cells. In addition, the potential interaction between fucoidan and filamin A (FLNA)-derived circular RNA (circFLNA) was predicted using bioinformatics databases and then confirmed in OSCC samples and cell lines. Indeed, fucoidan increased the expression of circFLNA in OSCC cell lines. Furthermore, both fucoidan and circFLNA could mediate the expression of key proteins related to cell growth, apoptosis, migration, and invasion. In conclusion, our research demonstrated that fucoidan might be considered as a potential natural drug in the treatment of OSCC patients by targeting circFLNA.

read more

PMID: 

Mar Drugs. 2019 Sep 8 ;17(9). Epub 2019 Sep 8. PMID: 31500384

Abstract Title: 

Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan.

Abstract: 

Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (,,,,and) both in U87MG and GBM8401 cells. Accordingly, the methylation of, a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition andinduction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo.

read more

PMID: 

J Agric Food Chem. 2019 Sep 17. Epub 2019 Sep 17. PMID: 31525874

Abstract Title: 

Xanthohumol suppresses NPC1L1 gene expression through down-regulation of HNF-4α and inhibits cholesterol uptake in Caco-2 cells.

Abstract: 

Xanthohumol (Xan) is a prenylated chalcone mainly found in hops, it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20μM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold; and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 μM) significantly inhibited cholesterol uptake by approximately 12% and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complexes formation, resulting in suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement forstatin therapy.

read more

PMID: 

Antioxidants (Basel). 2019 Sep 16 ;8(9). Epub 2019 Sep 16. PMID: 31527518

Abstract Title: 

Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells.

Abstract: 

BCR-ABL oncoprotein drives the initiation, promotion, and progression of chronic myelogenous leukemia (CML). Tyrosine kinase inhibitors are the first choice for CML therapy, however, BCR-ABL mediated drug resistance limits its clinical application and prognosis. A novel promising therapeutic strategy for CML therapy is to degrade BCR-ABL using small molecules. Antioxidant xanthohumol (XN) is a hop-derived prenylated flavonoid with multiple bioactivities. In this study, we showed XN could inhibit the proliferation, induce S phase cell cycle arrest, and stimulate apoptosis in K562 cells. XN degraded BCR-ABL in a concentration- and time-dependent manner, and the involved degradation pathway was caspase activation, while not autophagy induction or ubiquitin proteasome system (UPS) activation. Moreover, we revealed for the first time that XN could inhibit the UPS and autophagy in K562 cells, and the inhibitory effect of XN on autophagy could attenuate imatinib-induced autophagy and enhance the therapeutic efficiency of imatinib in K562 cells. Our present findings identified XN act as a degrader of BCR-ABL in K562 cells, and XN had potential to be developed as an alternate agent for CML therapy.

read more

PMID: 

Cancer Manag Res. 2019 ;11:5231-5242. Epub 2019 Jun 6. PMID: 31239776

Abstract Title: 

Tangeretin inhibits hepatocellular carcinoma proliferation and migration by promoting autophagy-related BECLIN1.

Abstract: 

Hepatocellular carcinoma (HCC) is a particularly prevalent type of liver cancer and is one of the deadliest malignancies in Asia. Tangeretin is a biological compound extracted from traditional Chinese herbs and has been shown to have potential antitumour properties; however, its mechanism remains largely unknown. Therefore, we sought to determine the role of Tangeretin in HepG2 cells subjected to antitumour treatment.Cell proliferation was quantified using CCK-8, EdU and colony formation assays, and cell migration was quantified using transwell migration and wound healing assays. Protein expression was assessed using Western blot analysis. Small interfering RNA was used to interfer protein expression. Immunoprecipitation was performed to detect the protein-protein interactions.Tangeretin decreased cell proliferation and increased G2/M arrest. Tangeretin decreased cell migration. Tangeretin increased the LC3II/LC3I ratio and decreased p62 expression in HepG2 cells. Furthermore, the knockdown of BECLIN1 expression in HepG2 cells partially converted the Tangeretin-induced inhibition of proliferation, migration and autophagy. In addition, Tangeretin activated the JNK1/Bcl-2 pathway and disturbed the interaction between Bcl-2 and BECLIN1. Together, our findings demonstrate that Tangeretin inhibited the proliferation and migration of HepG2 cells through JNK/Bcl-2/BECLIN1 pathway-mediated autophagy.Our study contributes to the understanding of the inhibitory mechanism of Tangeretin on HCC development.

read more

PMID: 

Pharmacology. 2019 ;104(3-4):187-195. Epub 2019 Jul 25. PMID: 31344704

Abstract Title: 

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats.

Abstract: 

BACKGROUND/AIMS: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats.METHODS: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism.RESULTS: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway.CONCLUSION: TAN might have potential as a therapeutic agent for the treatment of RA.

read more

PMID: 

J Endocr Soc. 2019 Sep 1 ;3(9):1715-1726. Epub 2019 Jul 25. PMID: 31528831

Abstract Title: 

Urinary Bisphenols and Obesity Prevalence Among U.S. Children and Adolescents.

Abstract: 

Bisphenol A (BPA) has been recognized as an endocrine disrupting chemical and identified as an obesogen. Although once ubiquitous, human exposure to BPA has been declining owing to its substitution with other bisphenols. Two structurally similar substitutes, bisphenol S (BPS) and bisphenol F (BPF), have raised similar concerns, although fewer studies have been conducted on these newer derivatives. We used data from the US National Health and Nutrition Examination Surveys from 2013 to 2016 to evaluate associations between BPA, BPS, and BPF and body mass outcomes among children and adolescents aged 6 to 19 years. Concentrations of BPA, BPS, and BPF were measured in spot urine samples using HPLC with tandem mass spectrometry. General obesity was defined as≥95th percentile of the age- and sex-standardized body mass index (BMI) z-scores according to the 2000 US norms. Abdominal obesity was defined as a waist circumference/height ratio of ≥0.5. BPA, BPS, and BPF were detected in 97.5%, 87.8%, and 55.2% of urine samples, respectively. Log-transformedurinary BPS concentrations were associated with an increased prevalence of general obesity (OR, 1.16; 95% CI, 1.02 to 1.32) and abdominal obesity (OR, 1.13; 95% CI, 1.02 to 1.27). BPF detection (vs not detected) was associated with an increased prevalence of abdominal obesity (OR, 1.29; 95% CI, 1.01 to 1.64) and continuous BMI z-score (= 0.10; 95% CI, 0.01 to 0.20). BPA and total bisphenols were not statistically significantly associated with general obesity, abdominal obesity, or any body mass outcome. These results suggest that BPA substitute chemicals are correlated with obesity in contemporary children.

read more

PMID: 

Toxicol Sci. 2019 Sep 18. Epub 2019 Sep 18. PMID: 31532523

Abstract Title: 

Prenatal exposure to bisphenol A, E and S induces transgenerational effects on male reproductive functions in mice.

Abstract: 

This study was performed to examine the transgenerational effects of bisphenol (BP) A analogues, BPE and BPS on male reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE or BPS (0.5 or 50µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 males. Prenatal exposure to BPA, BPE and BPS decreased sperm counts and/or motility and disrupted the progression of germ cell development as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F3 males. Dysregulated serum levels of estradiol-17β and testosterone, as well as expression of steroidogenic enzymes in F3 adult testis were also observed. In the neonatal testis, although apoptosis and DNA damage were not affected, mRNA levels of DNA methyltransferases, histone methyltransferases and their associated factors were increased by BP exposure. Furthermore, BP exposure induced immunoreactive expression of DNMT3A in Sertoli cells, strengthened DNMT3B and weakened H3K9me2 and H3K9me3 in germ cells of the neonataltestis, whereas DNMT1, H3K4me3 and H3K27ac were not affected. In adult testis, stage-specific DNMT3B was altered by BP exposure, although DNMT3A, H3K9me2 and H3K9me3 expression remained stable. These results suggest that prenatal exposure to BPA, BPE and BPS induces transgenerational effects on male reproductive functions probably due to altered epigenetic modification following disruption of DNMTs and histone marks in the neonatal and/or adult testis.

read more