Search Results

You are looking at 1 - 10 of 73 items for

  • Abstract: Bisphenol-A x
  • Abstract: Drugs x
Clear All Modify Search
Konstantin Yakimchuk Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

Search for other papers by Konstantin Yakimchuk in
Google Scholar
PubMed
Close
,
Chandrashekar Bangalore Revanna Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

Search for other papers by Chandrashekar Bangalore Revanna in
Google Scholar
PubMed
Close
,
Dan Huang Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

Search for other papers by Dan Huang in
Google Scholar
PubMed
Close
,
Jose Inzunza Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

Search for other papers by Jose Inzunza in
Google Scholar
PubMed
Close
, and
Sam Okret Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

Search for other papers by Sam Okret in
Google Scholar
PubMed
Close

Well-defined physiological functions of estrogens are mediated via nuclear estrogen receptors α (ESR1) and β (ESR2). With regard to hematological malignancies, expression of ESR2 has been found in both B and T cell lymphomas. In addition to endogenous estrogens or selective ESR2 agonists, ESR2 signaling may be affected by both environmental synthetic estrogen-mimicking compounds and dietary phytoestrogens. In the present study, we demonstrate that oral exposure with either the synthetic compound bisphenol A (BPA) or the dietary phytoestrogen genistein reduced the growth of grafted murine T cell (EG7) and human B cell (Granta-519 mantle cell) lymphomas which both express ESR2. Suppression of lymphoma growth was due to reduced proliferation (BPA and genistein) and induction of apoptosis (genistein). Inhibition of lymphoma growth was seen at a BPA dose of 50 µg/kg body weight (BW)/day considered to be safe human exposure dose or a genistein dose of 1 mg/kg BW/day orally, which is reached in soy-rich diets. Thus, our study indicates that the environmental xenoestrogens BPA and genistein have anti-proliferative effects on ESR2-expressing lymphomas. Our data suggest that phytoestrogens may be considered as a dietary supplement for lymphoma patients and possibly for prevention of lymphoid malignancies.

Open access
Daniel Alexander Hescheler Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany

Search for other papers by Daniel Alexander Hescheler in
Google Scholar
PubMed
Close
,
Milan Janis Michael Hartmann Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Cologne, Germany

Search for other papers by Milan Janis Michael Hartmann in
Google Scholar
PubMed
Close
,
Burkhard Riemann Department of Nuclear Medicine, University Hospital Münster, Münster, Germany

Search for other papers by Burkhard Riemann in
Google Scholar
PubMed
Close
,
Maximilian Michel Institute of Zoology, University of Cologne Germany, Cologne, Germany

Search for other papers by Maximilian Michel in
Google Scholar
PubMed
Close
,
Christiane Josephine Bruns Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Cologne, Germany

Search for other papers by Christiane Josephine Bruns in
Google Scholar
PubMed
Close
,
Hakan Alakus Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Cologne, Germany

Search for other papers by Hakan Alakus in
Google Scholar
PubMed
Close
, and
Costanza Chiapponi Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Cologne, Germany

Search for other papers by Costanza Chiapponi in
Google Scholar
PubMed
Close

Objective

Anaplastic thyroid cancer (ATC) is one of the most lethal human cancers with meager treatment options. We aimed to identify the targeted drugs already approved by the Food and Drug Administration (FDA) for solid cancer in general, which could be effective in ATC.

Design

Database mining.

Methods

FDA-approved drugs for targeted therapy were identified by screening the databases of MyCancerGenome and the National Cancer Institute. Drugs were linked to the target genes by querying Drugbank. Subsequently, MyCancerGenome, CIViC, TARGET and OncoKB were mined for genetic alterations which are predicted to lead to drug sensitivity or resistance. We searched the Cancer Genome Atlas database (TCGA) for patients with ATC and probed their sequencing data for genetic alterations which predict a drug response.

Results

In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified. Seventeen (52%) of 33 patients found in TCGA had at least one genetic alteration in targetable genes. The point mutation BRAF V600E was seen in 45% of patients. PIK3CA occurred in 18% of cases. Amplifications of ALK and SRC were detected in 3% of cases, respectively. Fifteen percent of the patients displayed a co-mutation of BRAF and PIK3CA. Besides BRAF-inhibitors, the PIK3CA-inhibitor copanlisib showed a genetically predicted response. The 146 (94%) remaining drugs showed no or low (under 4% cases) genetically predicted drug response.

Conclusions

While ATC carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.

Open access
Bernardo Maia Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Bernardo Maia in
Google Scholar
PubMed
Close
,
Leandro Kasuki Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Neuroendocrinology Division – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
Endocrinology Division – Hospital Federal de Bonsucesso, Rio de Janeiro Brazil

Search for other papers by Leandro Kasuki in
Google Scholar
PubMed
Close
, and
Mônica R Gadelha Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Neuroendocrinology Division – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
Neuropatology and Molecular Genetics Laboratory – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

Search for other papers by Mônica R Gadelha in
Google Scholar
PubMed
Close

Acromegaly is a systemic disease associated with increased morbidity and mortality. Most of these comorbidities can be prevented or delayed with adequate disease treatment. Although three modalities of treatment (surgery, medical treatment, and radiotherapy) are available and new drugs were approved in the last decades, there are still some patients that maintain disease activity despite treatment. Therefore, there is a need for novel therapies for acromegaly and for that purpose new formulations of currently used drugs and also new drugs are currently under study. In this review, we summarize the novel therapies for acromegaly.

Open access
Kristian Almstrup Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Kristian Almstrup in
Google Scholar
PubMed
Close
,
Hanne Frederiksen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Hanne Frederiksen in
Google Scholar
PubMed
Close
,
Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Anna-Maria Andersson in
Google Scholar
PubMed
Close
, and
Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Anders Juul in
Google Scholar
PubMed
Close

Puberty marks a transition period, which leads to the attainment of adult sexual maturity. Timing of puberty is a strongly heritable trait. However, large genetic association studies can only explain a fraction of the observed variability and striking secular trends suggest that lifestyle and/or environmental factors are important. Using liquid-chromatography tandem-mass-spectrometry, we measured endocrine-disrupting chemicals (EDCs; triclosan, bisphenol A, benzophenone-3, 2,4-dichlorophenol, 11 metabolites from 5 phthalates) in longitudinal urine samples obtained biannually from peri-pubertal children included in the COPENHAGEN puberty cohort. EDC levels were associated with blood DNA methylation profiles from 31 boys and 20 girls measured both pre- and post-pubertally. We found little evidence of single methylation sites that on their own showed association with urinary excretion levels of EDCs obtained either the same-day or measured as the yearly mean of dichotomized EDC levels. In contrast, methylation of several promoter regions was found to be associated with two or more EDCs, overlap with known gene–chemical interactions, and form a core network with genes known to be important for puberty. Furthermore, children with the highest yearly mean of dichotomized urinary phthalate metabolite levels were associated with higher promoter methylation of the thyroid hormone receptor interactor 6 gene (TRIP6), which again was mirrored by lower circulating TRIP6 protein levels. In general, the mean TRIP6 promoter methylation was mirrored by circulating TRIP6 protein levels. Our results provide a potential molecular mode of action of how exposure to environmental chemicals may modify pubertal development.

Open access
Amalie Carlsson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

Search for other papers by Amalie Carlsson in
Google Scholar
PubMed
Close
,
Kaspar Sørensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
The Child and Youth Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Kaspar Sørensen in
Google Scholar
PubMed
Close
,
Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

Search for other papers by Anna-Maria Andersson in
Google Scholar
PubMed
Close
,
Hanne Frederiksen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

Search for other papers by Hanne Frederiksen in
Google Scholar
PubMed
Close
, and
Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

Search for other papers by Anders Juul in
Google Scholar
PubMed
Close

Introduction

Bisphenol A and several of the most commonly used phthalates have been associated with adverse metabolic health effects such as obesity and diabetes. Therefore, we analyzed these man-made chemicals in first morning urine samples from 107 healthy normal-weight Danish children and adolescents.

Method

This was a cross-sectional study. Participants were recruited as part of the Copenhagen Puberty Study. The subjects were evaluated by an oral glucose tolerance test (OGTT), a dual-energy X-ray absorptiometry (DXA) scan, direct oxygen uptake measurement during cycle ergometry and fasting blood samples. First morning urine was collected and phthalate metabolites and BPA were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS) with prior enzymatic deconjugation. Individual chemical concentrations were divided into tertiles and analyzed in relation to biological outcome.

Results

Children in the lowest tertile of urinary BPA had significantly higher peak insulin levels during OGTT (P = 0.01), lower insulin sensitivity index (P < 0.01), higher leptin (P = 0.03), triglyceride (P < 0.01) and total cholesterol levels (P = 0.04), lower aerobic fitness (P = 0.02) and a tendency toward higher fat mass index (P = 0.1) compared with children in the highest tertile for uBPA. No significant differences in anthropometrics, body composition or glucose metabolism were associated with any of the phthalate metabolites measured.

Conclusion

This pilot study on healthy normal-weight children suggests an inverse association between BPA and insulin resistance. Our findings contrast other cross-sectional studies showing a positive association for BPA, which may be due to confounding or reverse causation because diet is an important source of both BPA exposure and obesity.

Open access
Maurício Martins da Silva Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Maurício Martins da Silva in
Google Scholar
PubMed
Close
,
Lueni Lopes Felix Xavier Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Lueni Lopes Felix Xavier in
Google Scholar
PubMed
Close
,
Carlos Frederico Lima Gonçalves Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Carlos Frederico Lima Gonçalves in
Google Scholar
PubMed
Close
,
Ana Paula Santos-Silva Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
NUMPEX, Campus Duque de Caxias, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Ana Paula Santos-Silva in
Google Scholar
PubMed
Close
,
Francisca Diana Paiva-Melo Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Francisca Diana Paiva-Melo in
Google Scholar
PubMed
Close
,
Mariana Lopes de Freitas Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Mariana Lopes de Freitas in
Google Scholar
PubMed
Close
,
Rodrigo Soares Fortunato Laboratory of Molecular Radiobiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Rodrigo Soares Fortunato in
Google Scholar
PubMed
Close
,
Leandro Miranda-Alves Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Leandro Miranda-Alves in
Google Scholar
PubMed
Close
, and
Andrea Claudia Freitas Ferreira Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
NUMPEX, Campus Duque de Caxias, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

Search for other papers by Andrea Claudia Freitas Ferreira in
Google Scholar
PubMed
Close

Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease.

Open access
Zhenyu Liu Department of Clinical Medicine, Beijing Luhe Hospital, Capital Medical University, Tongzhou District, Beijing, China

Search for other papers by Zhenyu Liu in
Google Scholar
PubMed
Close
,
Huixi Kong Department of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China

Search for other papers by Huixi Kong in
Google Scholar
PubMed
Close
, and
Baoyu Zhang Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Tongzhou District, Beijing, China

Search for other papers by Baoyu Zhang in
Google Scholar
PubMed
Close

To optimize the treatment plan for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia, this narrative literature review summarizes the effect of antidiabetic drugs on serum uric acid (SUA) levels using data from observational studies, prospective clinical trials, post hoc analyses, and meta-analyses. SUA is an independent risk factor for T2DM, and evidence has shown that patients with both gout and T2DM exhibit a mutually interdependent effect on higher incidences. We find that insulin and dipeptidyl peptidase 4 inhibitor (DPP-4i) except linagliptin could increase the SUA and other drugs including metformin, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), linagliptin, sodium–glucose cotransporter 2 inhibitors (SGLT2i), and α-glucosidase inhibitors have a reduction effect on SUA. We explain the mechanisms of different antidiabetic drugs above on SUA and analyze them compared with actual data. For sulfonylureas, meglitinides, and amylin analogs, the underlying mechanism remains unclear. We think the usage of linagliptin and SGLT2i is the most potentially effective treatment of patients with T2DM and hyperuricemia currently. Our review is a comprehensive summary of the effects of antidiabetic drugs on SUA, which includes actual data, the mechanisms of SUA regulation, and the usage rate of drugs.

Open access
Maria Luisa Brandi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Fondazione Italiana Ricerca sulle Malattie dell’Osso (FIRMO Onlus), Florence, Italy

Search for other papers by Maria Luisa Brandi in
Google Scholar
PubMed
Close
,
Stefania Bandinelli Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy

Search for other papers by Stefania Bandinelli in
Google Scholar
PubMed
Close
,
Teresa Iantomasi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

Search for other papers by Teresa Iantomasi in
Google Scholar
PubMed
Close
,
Francesca Giusti Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

Search for other papers by Francesca Giusti in
Google Scholar
PubMed
Close
,
Eleonora Talluri Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

Search for other papers by Eleonora Talluri in
Google Scholar
PubMed
Close
,
Giovanna Sini Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

Search for other papers by Giovanna Sini in
Google Scholar
PubMed
Close
,
Fabrizio Nannipieri Clinical Research, Abiogen Pharma, Pisa, Italy

Search for other papers by Fabrizio Nannipieri in
Google Scholar
PubMed
Close
,
Santina Battaglia Clinical Research, Abiogen Pharma, Pisa, Italy

Search for other papers by Santina Battaglia in
Google Scholar
PubMed
Close
,
Riccardo Giusti Clinical Research, Abiogen Pharma, Pisa, Italy

Search for other papers by Riccardo Giusti in
Google Scholar
PubMed
Close
,
Colin Gerard Egan CE Medical Writing SRLS, Pisa, Italy

Search for other papers by Colin Gerard Egan in
Google Scholar
PubMed
Close
, and
Luigi Ferrucci Longitudinal Study Section, Translation Gerontology Branch, National Institute on Aging, Baltimore, Maryland, USA

Search for other papers by Luigi Ferrucci in
Google Scholar
PubMed
Close

Objective

This study aimed to evaluate the association between the endocrine-disrupting chemical, bisphenol A (BPA) on circulating levels of 25-hydroxy vitamin D (25(OD)D) and other vitamin D metabolites in an elderly population in Italy.

Methods

This was a retrospective analysis of the InCHIANTI Biobank in Italy. The association between vitamin D metabolites namely 1,25(OH)D, 25(OH)D, parathyroid hormone (PTH) and BPA levels were evaluated. Multiple regression models were used to examine the association between predictor variables with 1,25(OH)D or 25(OH)D levels.

Results

Samples from 299 individuals aged 72.8 ± 15.7 years were examined. Mean levels of BPA, 1,25(OH)D and 25(OH)D were 351.2 ± 511.6 ng/dL, 43.7 ± 16.9 pg/mL and 20.2 ± 12.1 ng/mL, respectively. One hundred eighty individuals (60.2%) were deficient (<20 ng/mL) in 25(OH)D and this population also presented higher BPA levels (527.9 ± 1289.5 ng/dL vs 86.9 ± 116.8 ng/dL, P  < 0.0001). Univariate analysis revealed that BPA levels were negatively correlated with both 1,25(OH)D (r= −0.67, P  < 0.0001) and 25(OH)D (r= −0.69, P  < 0.0001). Multivariate regression revealed that PTH (β: −0.23, 95% CI: −0.34, −0.13, P  < 0.0001) and BPA (β: −0.25, 95% CI: −0.3, −0.19, P  < 0.0001) remained significantly associated with 25(OH)D levels while BPA was also associated with 1,25(OH)D levels (β: −0.19, 95% CI: −0.22, −0.15, P  < 0.0001). Receiver operating characteristic curve analysis showed that a BPA concentration of >113 ng/dL was the best cut-off to predict individuals deficient in 25(OH)D (area under the curve: 0.87, 95% CI: 0.82–0.90, P  < 0.0001).

Conclusion

The strong negative association between BPA and vitamin D in this elderly population warrants further investigation, particularly since this population is already at greatest risk of hypovitaminosis and fracture.

Open access
Nassim Ghaffari-Tabrizi-Wizsy Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Nassim Ghaffari-Tabrizi-Wizsy in
Google Scholar
PubMed
Close
,
Christina Angelika Passegger Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Christina Angelika Passegger in
Google Scholar
PubMed
Close
,
Laura Nebel Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Laura Nebel in
Google Scholar
PubMed
Close
,
Fabian Krismer Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Fabian Krismer in
Google Scholar
PubMed
Close
,
Gudrun Herzer-Schneidhofer Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Gudrun Herzer-Schneidhofer in
Google Scholar
PubMed
Close
,
Gert Schwach Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Gert Schwach in
Google Scholar
PubMed
Close
, and
Roswitha Pfragner Otto Loewi Research Center – Immunology and Pathophysiology, Medical University of Graz, Graz, Austria

Search for other papers by Roswitha Pfragner in
Google Scholar
PubMed
Close

Preclinical trials of medullary thyroid cancer (MTC) therapeutics require both in vitro and in vivo analyses. Human tumour xenografted rodent models, which are considered the ‘gold standard’ to study and validate the efficacy and toxicity of lead compounds before translation to clinical trials, are very expensive, subject to organismal variability and ethical controversies. The avian chorioallantoic membrane (CAM) assay provides an alternative versatile, cost-effective and ethically less objectionable short-term, in vivo model for reliable screening of drugs. In this work, we grafted two MTC cell lines and patient-derived MTC tumour samples onto the avian CAM and characterised the resulted tumours histologically and immunohistochemically. Our findings provide the evidence that the CAM assay is a suitable model for studying the pathophysiology of MTC and can even be used as in vivo system for drug testing.

Open access
Ruixin Hu School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Ruixin Hu in
Google Scholar
PubMed
Close
,
Yanting Yuan School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Yanting Yuan in
Google Scholar
PubMed
Close
,
Chaolong Liu School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Chaolong Liu in
Google Scholar
PubMed
Close
,
Ji Zhou School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Ji Zhou in
Google Scholar
PubMed
Close
,
Lixia Ji School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Lixia Ji in
Google Scholar
PubMed
Close
, and
Guohui Jiang School of pharmacy, Qing Dao University, Qingdao, China

Search for other papers by Guohui Jiang in
Google Scholar
PubMed
Close

In patients with type 2 diabetes mellitus (T2DM), the intestinal flora is out of balance and accompanied by leaky gut. The flora is characterized by an increase in mucus-degrading bacteria and a decrease in fiber-degrading bacteria. Short-chain fatty acids (SCFAs), as the major fiber-degrading bacteria fermentation, not only ameliorate the leaky gut, but also activate GPR43 to increase the mass of functional pancreatic β-cells and exert anti-inflammation effect. At present, the gut microbiota is considered as the potential target for anti-diabetes drugs, and how to reverse the imbalance of gut microbiota has become a therapeutic strategy for T2DM. This review briefly summarizes the drugs or compounds that have direct or potential therapeutic effects on T2DM by modulating the gut microbiota, including biguanides, isoquinoline alkaloids, stilbene and C7N-aminocyclic alcohols.

Open access