International Journal of Molecular Sciences

14 pages, 4664 KiB

Open AccessArticle

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma

by Caiqin Zhang^†, Yong Zhao^†, He Zhang, Xue Chen, Ningning Zhao, Dengxu Tan, Hai Zhang and Changhong Shi^*

¹ Laboratory Animal Center, the Fourth Military Medical University, Xi’an 710032, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1332; https://doi.org/10.3390/ijms18061332 - 21 Jun 2017

Cited by 39 | Viewed by 9882

Abstract

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a [...] Read more.

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 663 KiB

Open AccessReview

PD-1/PD-L1 Blockade Therapy for Tumors with Downregulated MHC Class I Expression

by Michal Šmahel

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Průmyslová 595, 25250 Vestec, Czech Republic

Int. J. Mol. Sci. 2017, 18(6), 1331; https://doi.org/10.3390/ijms18061331 - 21 Jun 2017

Cited by 59 | Viewed by 14791

Abstract

The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary [...] Read more.

The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host’s immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition. The potential for the use of a PD-1/PD-L1 blockade in the treatment of tumors with aberrant MHC class I expression is discussed, and some strategies of combination therapy are suggested. Full article

(This article belongs to the Special Issue Targeting Immune Checkpoints and Immunotherapy)

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16 pages, 2109 KiB

Open AccessArticle

Development of a High-Density SNP-Based Linkage Map and Detection of QTL for β-Glucans, Protein Content, Grain Yield per Spike and Heading Time in Durum Wheat

by Ilaria Marcotuli¹

, Agata Gadaleta^1,*, Giacomo Mangini²

, Antonio Massimo Signorile², Silvana Addolorata Zacheo², Antonio Blanco², Rosanna Simeone² and Pasqualina Colasuonno¹

¹ Department of Agricultural and Environmental Science, University of Bari “Aldo Moro”, Via G. Amendola 165/A, 70126 Bari, Italy

² Department of Soil, Plant and Food Sciences, Section of Genetic and Plant Breeding, University of Bari “Aldo Moro”, Via G. Amendola 165/A, 70126 Bari, Italy

Int. J. Mol. Sci. 2017, 18(6), 1329; https://doi.org/10.3390/ijms18061329 - 21 Jun 2017

Cited by 57 | Viewed by 7081

Abstract

High-density genetic linkage maps of crop species are particularly useful in detecting qualitative and quantitative trait loci for important agronomic traits and in improving the power of classical approaches to identify candidate genes. The aim of this study was to develop a high-density [...] Read more.

High-density genetic linkage maps of crop species are particularly useful in detecting qualitative and quantitative trait loci for important agronomic traits and in improving the power of classical approaches to identify candidate genes. The aim of this study was to develop a high-density genetic linkage map in a durum wheat recombinant inbred lines population (RIL) derived from two elite wheat cultivars and to identify, characterize and correlate Quantitative Trait Loci (QTL) for β-glucan, protein content, grain yield per spike and heading time. A dense map constructed by genotyping the RIL population with the wheat 90K iSelect array included 5444 single nucleotide polymorphism (SNP) markers distributed in 36 linkage groups. Data for β-glucan and protein content, grain yield per spike and heading time were obtained from replicated trials conducted at two locations in southern Italy. A total of 19 QTL were detected in different chromosome regions. In particular, three QTL for β-glucan content were detected on chromosomes 2A and 2B (two loci); eight QTL controlling grain protein content were detected on chromosomes 1B, 2B, 3B (two loci), 4A, 5A, 7A and 7B; seven QTL for grain yield per spike were identified on chromosomes 1A, 2B, 3A (two loci), 3B (two loci) and 6B; and one marker-trait association was detected on chromosome 2A for heading time. The last was co-located with a β-glucan QTL, and the two QTL appeared to be negatively correlated. A genome scan for genomic regions controlling the traits and SNP annotated sequences identified five putative candidate genes involved in different biosynthesis pathways (β-glucosidase, GLU1a; APETALA2, TaAP2; gigantea 3, TaGI3; 14-3-3 protein, Ta14A; and photoperiod sensitivity, Ppd-A1). This study provides additional information on QTL for important agronomic traits that could be useful for marker-assisted breeding to obtain new genotypes with commercial and nutritional relevance. Full article

(This article belongs to the Special Issue Glucan: New Perspectives on Biochemistry and Application)

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14 pages, 3932 KiB

Open AccessReview

dIvergEnt: How IgE Axis Contributes to the Continuum of Allergic Asthma and Anti-IgE Therapies

by Óscar Palomares¹, Silvia Sánchez-Ramón^2,3

, Ignacio Dávila⁴, Luis Prieto⁵, Luis Pérez de Llano⁶, Marta Lleonart⁷, Christian Domingo^8,* and Antonio Nieto⁹

¹ Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, 28040 Madrid, Spain

² Department of Clinical Immunology and Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, 28040 Madrid, Spain

³ Department of Microbiology I, Complutense University School of Medicine, 28040 Madrid, Spain

⁴ Allergy Service, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca (IBSAL), Biomedical and Diagnosis Science Department, Salamanca University School of Medicine, 37008 Salamanca, Spain

⁵ Department of Allergy and Immunology, University of Valencia and Dr. Peset University Hospital, 46017 Valencia, Spain

⁶ Neumology Service, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain

⁷ Novartis Farmacéutica, 08013 Barcelona, Spain

⁸ Pulmonary Service, Corporació Sanitària Parc Taulí, Department of Medicine, Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain

⁹ Pediatric Pulmonology & Allergy Unit, Children’s Hospital La Fe, 46026 Valencia, Spain

Int. J. Mol. Sci. 2017, 18(6), 1328; https://doi.org/10.3390/ijms18061328 - 21 Jun 2017

Cited by 56 | Viewed by 10470

Abstract

Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients [...] Read more.

Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches. Attempts have been made to identify the most relevant molecular and cellular biomarkers underlying the immunopathophysiological mechanisms of the disease. For almost 50 years, immunoglobulin E (IgE) has been identified as a central factor in allergic asthma, due to its allergen-specific nature. Many of the mechanisms of the inflammatory cascade underlying allergic asthma have already been elucidated, and IgE has been shown to play a fundamental role in the triggering, development, and chronicity of the inflammatory responses within the disease. Blocking IgE with monoclonal antibodies such as omalizumab have demonstrated their efficacy, effectiveness, and safety in treating allergic asthma. A better understanding of the multiple contributions of IgE to the inflammatory continuum of asthma could contribute to the development of novel therapeutic strategies for the disease. Full article

(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)

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30 pages, 1313 KiB

Open AccessReview

Fucaceae: A Source of Bioactive Phlorotannins

by Marcelo D. Catarino

, Artur M. S. Silva

and Susana M. Cardoso^*

Department of Chemistry & Organic Chemistry, Natural Products and Food Stuffs Research Unit (QOPNA), University of Aveiro, Aveiro 3810-193, Portugal

Int. J. Mol. Sci. 2017, 18(6), 1327; https://doi.org/10.3390/ijms18061327 - 21 Jun 2017

Cited by 114 | Viewed by 9580

Abstract

Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These [...] Read more.

Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These macroalgae are endowed with several phytochemicals of great industrial interest from which phlorotannins, a class of marine-exclusive polyphenols, have gathered much attention during the last few years due to their numerous possible therapeutic properties. These compounds are very abundant in brown seaweeds such as Fucaceae and have been demonstrated to possess numerous health-promoting properties, including antioxidant effects through scavenging of reactive oxygen species (ROS) or enhancement of intracellular antioxidant defenses, antidiabetic properties through their acarbose-like activity, stimulation of adipocytes glucose uptake and protection of β-pancreatic cells against high-glucose oxidative stress; anti-inflammatory effects through inhibition of several pro-inflammatory mediators; antitumor properties by activation of apoptosis on cancerous cells and metastasis inhibition, among others. These multiple health properties render phlorotannins great potential for application in numerous therapeutical approaches. This review addresses the major contribution of phlototannins for the biological effects that have been described for seaweeds from Fucaceae. In addition, the bioavailability of this group of phenolic compounds is discussed. Full article

(This article belongs to the Special Issue Biological Activity of Natural Secondary Metabolite Products)

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17 pages, 1099 KiB

Open AccessArticle

Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice

by María A. Aguilar^*

, Juan Carlos Ledesma^*, Marta Rodríguez-Arias, Carles Penalva, Carmen Manzanedo, José Miñarro and M. Carmen Arenas

Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain

Int. J. Mol. Sci. 2017, 18(6), 1326; https://doi.org/10.3390/ijms18061326 - 21 Jun 2017

Cited by 15 | Viewed by 6921

Abstract

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from [...] Read more.

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice. Full article

(This article belongs to the Special Issue Cannabinoid Signaling in Nervous System)

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15 pages, 1794 KiB

Open AccessReview

New Insights in Thyroid Cancer and p53 Family Proteins

by Livia Manzella^1,*, Stefania Stella¹, Maria Stella Pennisi¹, Elena Tirrò¹

, Michele Massimino¹, Chiara Romano¹, Adriana Puma¹, Martina Tavarelli² and Paolo Vigneri¹

¹ Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy

² Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi Nesima Medical Center, University of Catania, 95122 Catania, Italy

Int. J. Mol. Sci. 2017, 18(6), 1325; https://doi.org/10.3390/ijms18061325 - 21 Jun 2017

Cited by 69 | Viewed by 9589

Abstract

Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured [...] Read more.

Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy. Therefore, novel and more effective therapies for these aggressive neoplasias are urgently needed. Whereas most genetic events underlying the pathogenesis of well-differentiated thyroid cancers have been identified, the molecular mechanisms that generate undifferentiated thyroid carcinomas are still unclear. To date, one of the best-characterized genetic alterations leading to the development of poorly differentiated thyroid tumors is the loss of the p53 tumor suppressor gene. In addition, the existence of a complex network among p53 family members (p63 and p73) and their interactions with other factors that promote thyroid cancer progression has been well documented. In this review, we provide an update on the current knowledge of the role of p53 family proteins in thyroid cancer and their possible use as a therapeutic target for the treatment of the most aggressive variants of this disease. Full article

(This article belongs to the Special Issue Current Knowledge in Thyroid Cancer—From Bench to Bedside)

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12 pages, 875 KiB

Open AccessReview

Immune Checkpoints as a Target for Colorectal Cancer Treatment

by Alessandro Passardi¹

, Matteo Canale², Martina Valgiusti¹ and Paola Ulivi^2,*

¹ Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy

² Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy

Int. J. Mol. Sci. 2017, 18(6), 1324; https://doi.org/10.3390/ijms18061324 - 21 Jun 2017

Cited by 115 | Viewed by 11090

Abstract

Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, [...] Read more.

Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies. We present an updated review of the biological background and clinical development of immune checkpoint inhibitors in colorectal cancer (CRC). Early trial results on PD1 and PD-L1 blockade appear promising, especially in CRC patients with microsatellite instability (MSI). Clinical trials are ongoing to confirm these preliminary results, evaluate combination strategies and identify biomarkers to predict which patients are most likely to benefit from, or show resistance to, the effects of checkpoint inhibition. Full article

(This article belongs to the Special Issue Latest Advances in Colorectal Cancer Research: Molecular Mechanisms and Therapies)

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17 pages, 2271 KiB

Open AccessArticle

Diverse Regulation of Vitamin D Receptor Gene Expression by 1,25-Dihydroxyvitamin D and ATRA in Murine and Human Blood Cells at Early Stages of Their Differentiation

by Sylwia Janik^1,†, Urszula Nowak^2,†, Agnieszka Łaszkiewicz¹, Anastasiia Satyr², Michał Majkowski¹, Aleksandra Marchwicka², Łukasz Śnieżewski¹, Klaudia Berkowska², Marian Gabryś³, Małgorzata Cebrat¹ and Ewa Marcinkowska^2,*

¹ Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Weigla 12, 53-114 Wrocław, Poland

² Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland

³ First Department of Obstetrics and Gynecology, Wrocław Medical University, Chałubińskiego 3, 50-368 Wrocław, Poland

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1323; https://doi.org/10.3390/ijms18061323 - 21 Jun 2017

Cited by 17 | Viewed by 8647

Abstract

Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, [...] Read more.

Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, as the fusion of RARα gene with PML gene initiates acute promyelocytic leukemia where differentiation of the myeloid lineage is blocked, followed by an uncontrolled proliferation of leukemic blasts. RARα takes part in regulation of VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells. This is why we decided to examine the effects of the combination of 1,25D and all-trans-retinoic acid (ATRA) on VDR gene expression in normal human and murine blood cells at various steps of their development. We tested the expression of VDR and regulation of this gene in response to 1,25D or ATRA, as well as transcriptional activities of nuclear receptors VDR and RARs in human and murine blood cells. We discovered that regulation of VDR expression in humans is different from in mice. In human blood cells at early stages of their differentiation ATRA, but not 1,25D, upregulates the expression of VDR. In contrast, in murine blood cells 1,25D, but not ATRA, upregulates the expression of VDR. VDR and RAR receptors are present and transcriptionally active in blood cells of both species, especially at early steps of blood development. Full article

(This article belongs to the Special Issue The Biology and Treatment of Myeloid Leukaemias)

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14 pages, 3252 KiB

Open AccessArticle

Identification and Validation of Reference Genes for Seashore Paspalum Response to Abiotic Stresses

by Yu Liu¹, Jun Liu¹, Lei Xu¹, Hui Lai¹, Yu Chen^1,*, Zhimin Yang¹ and Bingru Huang^2,*

¹ College of Agro-grassland Science, Nanjing Agricultural University, Nanjing 210095, China

² Department of Plant Biology and Pathology, Rutgers University, New Brunswick, NJ 08901, USA

Int. J. Mol. Sci. 2017, 18(6), 1322; https://doi.org/10.3390/ijms18061322 - 21 Jun 2017

Cited by 40 | Viewed by 5066

Abstract

Seashore paspalum (Paspalum vaginatum) is among the most salt- and cadmium-tolerant warm-season perennial grass species widely used as turf or forage. The objective of this study was to select stable reference genes for quantitative real-time polymerase chain reaction (qRT-PCR) analysis of [...] Read more.

Seashore paspalum (Paspalum vaginatum) is among the most salt- and cadmium-tolerant warm-season perennial grass species widely used as turf or forage. The objective of this study was to select stable reference genes for quantitative real-time polymerase chain reaction (qRT-PCR) analysis of seashore paspalum in response to four abiotic stresses. The stability of 12 potential reference genes was evaluated by four programs (geNorm, NormFinder, BestKeeper, and RefFinder). U2AF combined with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) showed stable expression in Cd-treated leaves and cold-treated roots. U2AF and FBOX were the most stable reference genes in Cd-treated roots and cold-treated leaves. In Polyethylene Glycol (PEG)- or salt-treated roots, the reference gene U2AF paired with either ACT or CYP were stable. SAND and CACS exhibited the most stability in salt-treated leaves, and combining UPL, PP2A, and EF1a was most suitable for PEG-treated leaves. The stability of U2AF and instability of UPL and TUB was validated by analyzing the expression levels of four target genes (MT2a, VP1, PIP1, and Cor413), and were shown to be capable of detecting subtle changes in expression levels of the target genes in seashore paspalum. This study demonstrated that FBOX, U2AF, and PP2A could be used in future molecular studies that aim to understand the mechanisms of abiotic stress tolerance in seashore paspalum. Full article

(This article belongs to the Section Molecular Plant Sciences)

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17 pages, 1108 KiB

Open AccessReview

Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction

by Arunkumar E. Achari and Sushil K. Jain^*

Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA

Int. J. Mol. Sci. 2017, 18(6), 1321; https://doi.org/10.3390/ijms18061321 - 21 Jun 2017

Cited by 911 | Viewed by 42865

Abstract

Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can [...] Read more.

Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review. Full article

(This article belongs to the Special Issue Adipokines)

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14 pages, 3249 KiB

Open AccessArticle

Hypoxic Preconditioning Promotes the Bioactivities of Mesenchymal Stem Cells via the HIF-1α-GRP78-Akt Axis

by Jun Hee Lee¹, Yeo Min Yoon² and Sang Hun Lee^2,3,*

¹ Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA

² Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 336-745, Korea

³ Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Korea

Int. J. Mol. Sci. 2017, 18(6), 1320; https://doi.org/10.3390/ijms18061320 - 21 Jun 2017

Cited by 124 | Viewed by 7977

Abstract

Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such [...] Read more.

Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α. Hypoxia-induced GRP78 promoted the proliferation and migration potential of MSCs through the HIF-1α-GRP78-Akt signal axis. In a murine hind-limb ischemia model, hypoxic preconditioning enhanced the survival and proliferation of transplanted MSCs through suppression of the cell death signal pathway and augmentation of angiogenic cytokine secretion. These effects were regulated by GRP78. Our findings indicate that hypoxic preconditioning promotes survival, proliferation, and angiogenic cytokine secretion of MSCs via the HIF-1α-GRP78-Akt signal pathway, suggesting that hypoxia-preconditioned MSCs might provide a therapeutic strategy for MSC-based therapies and that GRP78 represents a potential target for the development of functional MSCs. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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17 pages, 20655 KiB

Open AccessArticle

The Arabidopsis GPR1 Gene Negatively Affects Pollen Germination, Pollen Tube Growth, and Gametophyte Senescence

by Xiao Yang

, Qinying Zhang, Kun Zhao

, Qiong Luo, Shuguang Bao, Huabin Liu and Shuzhen Men^*

Department of Plant Biology and Ecology, College of Life Sciences, Nankai University, Tianjin 300071, China

Int. J. Mol. Sci. 2017, 18(6), 1303; https://doi.org/10.3390/ijms18061303 - 21 Jun 2017

Cited by 15 | Viewed by 9255

Abstract

Genes essential for gametophyte development and fertilization have been identified and studied in detail; however, genes that fine-tune these processes are largely unknown. Here, we characterized an unknown Arabidopsis gene, GTP-BINDING PROTEIN RELATED1 (GPR1). GPR1 is specifically expressed in ovule, pollen, [...] Read more.

Genes essential for gametophyte development and fertilization have been identified and studied in detail; however, genes that fine-tune these processes are largely unknown. Here, we characterized an unknown Arabidopsis gene, GTP-BINDING PROTEIN RELATED1 (GPR1). GPR1 is specifically expressed in ovule, pollen, and pollen tube. Enhanced green fluorescent protein-tagged GPR1 localizes to both nucleus and cytoplasm, and it also presents in punctate and ring-like structures. gpr1 mutants exhibit no defect in gametogenesis and seed setting, except that their pollen grains are pale in color. Scanning electron microscopy analyses revealed a normal patterned but thinner exine on gpr1 pollen surface. This may explain why gpr1 pollen grains are pale. We next examined whether GPR1 mutation affects post gametogenesis processes including pollen germination, pollen tube growth, and ovule senescence. We found that gpr1 pollen grains germinated earlier, and their pollen tubes elongated faster. Emasculation assay revealed that unfertilized gpr1 pistil expressed the senescence marker P_BFN1:GUS (GUS: a reporter gene that encodes β-glucuronidase) one-day earlier than the wild type pistil. Consistently, ovules and pollen grains of gpr1 mutants showed lower viability than those of the wild type at 4 to 5 days post anthesis. Together, these data suggest that GPR1 functions as a negative regulator of pollen germination, pollen tube growth, and gametophyte senescence to fine-tune the fertilization process. Full article

(This article belongs to the Section Molecular Plant Sciences)

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17 pages, 656 KiB

Open AccessReview

The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer’s Disease Neuropathology

by Nadia Canu^1,2,†, Giuseppina Amadoro^3,†, Viviana Triaca^2,†, Valentina Latina³, Valentina Sposato⁴, Veronica Corsetti⁴, Cinzia Severini², Maria Teresa Ciotti² and Pietro Calissano^4,*

¹ Department of System Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00137 Rome, Italy

² Institute of Cellular Biology and Neurobiology, National Council of Research Rome, Via del Fosso del Fiorano 64, 00143 Rome, Italy

³ Institute of Translational Pharmacology, National Research Council (CNR) Rome, Via Fosso del Cavaliere 100, 00133 Rome, Italy

⁴ European Brain Research Institute Rome, Via del Fosso del Fiorano 64, 00143 Rome, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1319; https://doi.org/10.3390/ijms18061319 - 20 Jun 2017

Cited by 54 | Viewed by 11444

Abstract

Dysfunction of nerve growth factor (NGF) and its high-affinity Tropomyosin receptor kinase A (TrkA) receptor has been suggested to contribute to the selective degeneration of basal forebrain cholinergic neurons (BFCN) associated with the progressive cognitive decline in Alzheimer's disease (AD). The aim of [...] Read more.

Dysfunction of nerve growth factor (NGF) and its high-affinity Tropomyosin receptor kinase A (TrkA) receptor has been suggested to contribute to the selective degeneration of basal forebrain cholinergic neurons (BFCN) associated with the progressive cognitive decline in Alzheimer's disease (AD). The aim of this review is to describe our progress in elucidating the molecular mechanisms underlying the dynamic interplay between NGF/TrkA signaling and amyloid precursor protein (APP) metabolism within the context of AD neuropathology. This is mainly based on the finding that TrkA receptor binding to APP depends on a minimal stretch of ~20 amino acids located in the juxtamembrane/extracellular domain of APP that carries the α- and β-secretase cleavage sites. Here, we provide evidence that: (i) NGF could be one of the “routing” proteins responsible for modulating the metabolism of APP from amyloidogenic towards non-amyloidogenic processing via binding to the TrkA receptor; (ii) the loss of NGF/TrkA signaling could be linked to sporadic AD contributing to the classical hallmarks of the neuropathology, such as synaptic loss, β-amyloid peptide (Aβ) deposition and tau abnormalities. These findings will hopefully help to design therapeutic strategies for AD treatment aimed at preserving cholinergic function and anti-amyloidogenic activity of the physiological NGF/TrkA pathway in the septo-hippocampal system. Full article

(This article belongs to the Special Issue Neurotrophic Factors—Historical Perspective and New Directions)

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18 pages, 3030 KiB

Open AccessArticle

Fluorescence Analysis of Vitamin D Receptor Status of Circulating Tumor Cells (CTCS) in Breast Cancer: From Cell Models to Metastatic Patients

by Xi Zhang¹, Simone Hofmann¹, Brigitte Rack¹, Nadia Harbeck¹, Udo Jeschke¹

and Sophie Sixou^1,2,*

¹ Department of Obstetrics and Gynaecology, Breast Center, Ludwig-Maximilians University of Munich (LMU), Maistrasse 11, Munich 80337, Germany

² Faculty of Pharmacy, University Paul Sabatier Toulouse III, Toulouse cedex 09 31062, France

Int. J. Mol. Sci. 2017, 18(6), 1318; https://doi.org/10.3390/ijms18061318 - 20 Jun 2017

Cited by 11 | Viewed by 7282

Abstract

The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early [...] Read more.

The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early and metastatic BC. Consequently, an evaluation of VDR expression in the CTCs of BC patients may allow optimization of their treatment. As an attempt to profile and subtype the CTCs of metastatic patients, we established an innovative fluorescence technique using nine BC cell lines to visualize, define, and compare their individual VDR status. Afterwards, we tested the CTC presence and VDR expression in blood samples (cytospins) collected from 23 metastatic BC patients. The results demonstrated major differences in the VDR levels among the nine cell lines, and VDR positive CTCs were detected in 46% of CTC-positive patients, with a total of 42 CTCs individually analyzed. Due to the limited number of patients in this study, no correlation between VDR expression and BC subtype classification (according to estrogen receptor (ER), progesterone receptor (PR) and HER2) could be determined, but our data support the view that VDR evaluation is a potential new prognostic biomarker to help in the optimization of therapy management for BC patients. Full article

(This article belongs to the Special Issue Vitamin D and Its Analogues: New Insights on Biological Effects and Therapeutic Uses)

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16 pages, 2068 KiB

Open AccessArticle

The Protease Inhibitor CI2c Gene Induced by Bird Cherry-Oat Aphid in Barley Inhibits Green Peach Aphid Fecundity in Transgenic Arabidopsis

by Aleksandra Losvik^†, Lisa Beste^†, Sara Mehrabi and Lisbeth Jonsson^*

¹ Department of Ecology, Environment and Plant Sciences, Stockholm University, 106 91 Stockholm, Sweden

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1317; https://doi.org/10.3390/ijms18061317 - 20 Jun 2017

Cited by 14 | Viewed by 5254

Abstract

Aphids are phloem feeders that cause large damage globally as pest insects. They induce a variety of responses in the host plant, but not much is known about which responses are promoting or inhibiting aphid performance. Here, we investigated whether one of the [...] Read more.

Aphids are phloem feeders that cause large damage globally as pest insects. They induce a variety of responses in the host plant, but not much is known about which responses are promoting or inhibiting aphid performance. Here, we investigated whether one of the responses induced in barley by the cereal aphid, bird cherry-oat aphid (Rhopalosiphum padi L.) affects aphid performance in the model plant Arabidopsis thaliana L. A barley cDNA encoding the protease inhibitor CI2c was expressed in A. thaliana and aphid performance was studied using the generalist green peach aphid (Myzus persicae Sulzer). There were no consistent effects on aphid settling or preference or on parameters of life span and long-term fecundity. However, short-term tests with apterous adult aphids showed lower fecundity on three of the transgenic lines, as compared to on control plants. This effect was transient, observed on days 5 to 7, but not later. The results suggest that the protease inhibitor is taken up from the tissue during probing and weakly inhibits fecundity by an unknown mechanism. The study shows that a protease inhibitor induced in barley by an essentially monocot specialist aphid can inhibit a generalist aphid in transgenic Arabidopsis. Full article

(This article belongs to the Special Issue Plant Defense Genes Against Biotic Stresses)

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17 pages, 2972 KiB

Open AccessReview

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

by Leticia De las Vecillas Sánchez^1,2, Leila A. Alenazy^1,3,4, Marlene Garcia-Neuer¹ and Mariana C. Castells^1,*

¹ Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

² Department of Allergy, Marqués de Valdecilla University Hospital-IDIVAL, 39011 Santander, Spain

³ Department of Medicine, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia

⁴ Master of Medical Sciences in Immunology Program, Harvard Medical School, Boston, MA 02115, USA

Int. J. Mol. Sci. 2017, 18(6), 1316; https://doi.org/10.3390/ijms18061316 - 20 Jun 2017

Cited by 107 | Viewed by 15662

Abstract

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross [...] Read more.

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications. Full article

(This article belongs to the Special Issue Drug Hypersensitivity)

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10 pages, 1093 KiB

Open AccessReview

The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes

by Anna Bilska-Wilkosz^*

, Małgorzata Iciek, Magdalena Górny and Danuta Kowalczyk-Pachel

Chair of Medical Biochemistry, Jagiellonian University Collegium Medicum ,7 Kopernika Street, Kraków 31-034, Poland

Int. J. Mol. Sci. 2017, 18(6), 1315; https://doi.org/10.3390/ijms18061315 - 20 Jun 2017

Cited by 27 | Viewed by 8399

Abstract

Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide [...] Read more.

Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide oxidation pathway. In this review, we discuss the current state of knowledge on the interactions between hydrogen sulfide and hemoglobin, myoglobin and neuroglobin and postulate that thiosulfate is a metabolically important product of this processes. Hydrogen sulfide oxidation by ferric hemoglobin, myoglobin and neuroglobin has been defined as a non-canonical hydrogen sulfide oxidation pathway. Until recently, it appeared that the goal of thiosulfate production was to delay irreversible oxidation of hydrogen sulfide to sulfate excreted in urine; while thiosulfate itself was only an intermediate, transient metabolite on the hydrogen sulfide oxidation pathway. In the light of data presented in this paper, it seems that thiosulfate is a molecule that plays a prominent role in the human body. Thus, we hope that all these findings will encourage further studies on the role of hemoproteins in the formation of this undoubtedly fascinating molecule and on the mechanisms responsible for its biological activity in the human body. Full article

(This article belongs to the Special Issue Metalloproteins 2017)

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15 pages, 913 KiB

Open AccessReview

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

by Jinyoung Won^1,2,3,†, Yunho Jin^1,2,3,†, Jeonghyun Choi^1,2,3, Sookyoung Park^2,3,4, Tae Ho Lee⁵, Sang-Rae Lee⁶, Kyu-Tae Chang^6,* and Yonggeun Hong^1,2,3,4,*

¹ Department of Rehabilitation Science, Graduate School of Inje University, Gimhae 50834, Korea

² Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae 50834, Korea

³ Biohealth Products Research Center (BPRC), Inje University, Gimhae 50834, Korea

⁴ Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Inje University, Gimhae 50834, Korea

⁵ Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

⁶ National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 28116, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1314; https://doi.org/10.3390/ijms18061314 - 20 Jun 2017

Cited by 19 | Viewed by 9352

Abstract

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety [...] Read more.

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm. Full article

(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)

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10 pages, 1032 KiB

Open AccessReview

Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

by Kazuhiro Takahashi^1,*

, Koji Ohba¹, Kazuki Tajima¹, Tsuguo Nishijima² and Shigeru Sakurai²

¹ Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan

² Division of Behavioral Sleep Medicine, Iwate Medical University School of Medicine, Morioka, Iwate 020-0850, Japan

Int. J. Mol. Sci. 2017, 18(6), 1313; https://doi.org/10.3390/ijms18061313 - 20 Jun 2017

Cited by 14 | Viewed by 6224

Abstract

(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and [...] Read more.

(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS). Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(P)RR levels in OSAS. Full article

(This article belongs to the Special Issue Selected Papers from the Renin–Angiotensin–Aldosterone System (RAAS)2016: Official Satellite of ISH2016, from September 23 to 24 in Tokyo, Japan)

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10 pages, 1168 KiB

Open AccessArticle

Synthesis and Biodegradation of Poly(l-lactide-co-β-propiolactone)

by Yuushou Nakayama^1,*

, Kazuki Aihara¹, Zhengguo Cai²

, Takeshi Shiono^1,*

and Chikara Tsutsumi³

¹ Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi-Hiroshima 739-8527, Japan

² State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Material Science and Engineering, Donghua University, Shanghai 201620, China

³ Department of Applied Chemistry and Biotechnology, Niihama National College of Technology, Niihama 792-8580, Japan

Int. J. Mol. Sci. 2017, 18(6), 1312; https://doi.org/10.3390/ijms18061312 - 20 Jun 2017

Cited by 13 | Viewed by 6029

Abstract

Although the copolymerizations of l-lactide (LA) with seven- or six-membered ring lactones have been extensively studied, the copolymerizations of LA with four-membered ring lactones have scarcely been reported. In this work, we studied the copolymerization of LA with β-propiolactone (PL) and the [...] Read more.

Although the copolymerizations of l-lactide (LA) with seven- or six-membered ring lactones have been extensively studied, the copolymerizations of LA with four-membered ring lactones have scarcely been reported. In this work, we studied the copolymerization of LA with β-propiolactone (PL) and the properties of the obtained copolymers. The copolymerization of LA with PL was carried out using trifluoromethanesulfonic acid as a catalyst and methanol as an initiator to produce poly(LA-co-PL) with M_n of ~50,000 and PL-content of 6–67 mol %. The T_g values of the copolymers were rapidly lowered with increasing PL-contents. The T_m and ΔH_m of the copolymers gradually decreased with increasing PL-contents, indicating their decreased crystallinity. Biodegradation test of the copolymers in compost demonstrated their improved biodegradability in comparison with the homopolymer of LA. Full article

(This article belongs to the Special Issue Biodegradable Materials 2017)

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13 pages, 657 KiB

Open AccessArticle

Sexually Transmitted Infections: A Novel Screening Strategy for Improving Women’s Health in Vulnerable Populations

by Elena R. Frati¹

, Ester Fasoli¹, Marianna Martinelli¹

, Daniela Colzani¹, Silvia Bianchi¹, Luciana Carnelli², Antonella Amendola^1,3,4, Pierfranco Olivani⁵ and Elisabetta Tanzi^1,3,4,*

¹ Department of Biomedical Sciences for Health, University of Milan, Via C. Pascal 36, 20133 Milan, Italy

² Lega Italiana per la Lotta contro i Tumori (LILT), Section of Milan, Viale Molise 5, 20137 Milan, Italy

³ Coordinated Research Center “EpiSoMI”, University of Milan, Via C. Pascal 36, 20133 Milan, Italy

⁴ CIRI-IV, Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16100 Genoa, Italy

⁵ NAGA Centre, Associazione Volontaria di Assistenza Socio-Sanitaria e per i Diritti di Cittadini Stranieri, Rom e Sinti, Via L. L. Zamenhof 7/A, 20136 Milan, Italy

Int. J. Mol. Sci. 2017, 18(6), 1311; https://doi.org/10.3390/ijms18061311 - 20 Jun 2017

Cited by 18 | Viewed by 5579

Abstract

Background: Migrant women are one of the most vulnerable population to health problems and well-being. This study aimed at implementing a counseling and preventive strategy for sexually transmitted infections (STIs) in undocumented migrant women in Milan, Italy. Methods: Women (ages 18–65) were enrolled [...] Read more.

Background: Migrant women are one of the most vulnerable population to health problems and well-being. This study aimed at implementing a counseling and preventive strategy for sexually transmitted infections (STIs) in undocumented migrant women in Milan, Italy. Methods: Women (ages 18–65) were enrolled at the NAGA Centre (2012–2013) and asked for a urine sample in order to carry out molecular detection of Human papillomavirus (HPV), Chlamydia trachomatis (Ct), Trichomonas vaginalis (Tv), Neisseria gonorrhoeae (Ng)-DNA. Socio-demographic and sexual behavior information were collected. All HPV/Ct+ women were offered Pap tests and/or were prescribed antibiotic treatment. Results: 537/757 women participated in the study (acceptability rate: 70.9%). Most of the women were from Latin America (45.6%) and Eastern Europe (30.7%); >60% of them had stable partners, did not use contraception and had had at least one pregnancy. The prevalence rates of HPV, Ct, Tv and Ng infections were 24.2%, 7.8%, 4.8% and 0%, respectively. In all, 43.2% of the positive women agreed to undergo a gynecological examination and accepted suitable treatment. Conclusions: This study shows an overall high prevalence of STIs in undocumented migrant women in Milan. The screening strategy based on counseling and urine testing contributed to the successfully high acceptability rate. More appropriate health services that adequately address all aspects of women’s health are required. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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27 pages, 359 KiB

Open AccessReview

Microbiota, Inflammation and Colorectal Cancer

by Cécily Lucas, Nicolas Barnich

and Hang Thi Thu Nguyen^*

M2iSH, UMR 1071 Inserm, University of Clermont Auvergne, INRA USC 2018, Clermont-Ferrand 63001, France

Int. J. Mol. Sci. 2017, 18(6), 1310; https://doi.org/10.3390/ijms18061310 - 20 Jun 2017

Cited by 252 | Viewed by 16188

Abstract

Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the [...] Read more.

Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment. Full article

(This article belongs to the Special Issue Inflammation and Cancer)

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15 pages, 3141 KiB

Open AccessArticle

Gene Expression Profiling Reveals Potential Players of Left-Right Asymmetry in Female Chicken Gonads

by Zhiyi Wan^1,†, Yanan Lu^1,†, Lei Rui¹, Xiaoxue Yu¹

, Fang Yang², Chengfang Tu³ and Zandong Li^1,*

¹ State key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China

² College of Life Sciences, Peking University, Beijing 100871, China

³ Annoroad Gene Technology Co., Ltd., Beijing 100176, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1299; https://doi.org/10.3390/ijms18061299 - 20 Jun 2017

Cited by 12 | Viewed by 5445

Abstract

Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was [...] Read more.

Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was carried out on total RNA harvested from the left and right gonads on embryonic day 6 (E6), E12, and post-hatching day 1 (D1). By comparing the gene expression profiles between the left and right gonads, 347 differentially expressed genes (DEGs) were obtained on E6, 3730 were obtained on E12, and 2787 were obtained on D1. Side-specific genes were primarily derived from the autosome rather than the sex chromosome. Gene ontology and pathway analysis showed that the DEGs were most enriched in the Piwi-interactiing RNA (piRNA) metabolic process, germ plasm, chromatoid body, P granule, neuroactive ligand-receptor interaction, microbial metabolism in diverse environments, and methane metabolism. A total of 111 DEGs, five gene ontology (GO) terms, and three pathways were significantly different between the left and right gonads among all the development stages. We also present the gene number and the percentage within eight development-dependent expression patterns of DEGs in the left and right gonads of female chicken. Full article

(This article belongs to the Section Biochemistry)

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9 pages, 1384 KiB

Open AccessArticle

Centrosomal Protein 70 Is a Mediator of Paclitaxel Sensitivity

by Xingjuan Shi^1,*, Yujue Wang¹, Xiaoou Sun², Chan Wang¹, Peng Jiang¹, Yu Zhang¹, Qinghai Huang¹, Xiangdong Liu¹, Dengwen Li³, Jun Zhou^3,4 and Min Liu^4,*

¹ Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing 210096, China

² School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China

³ State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

⁴ Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China

Int. J. Mol. Sci. 2017, 18(6), 1267; https://doi.org/10.3390/ijms18061267 - 20 Jun 2017

Cited by 7 | Viewed by 4500

Abstract

Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug [...] Read more.

Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. Here we provide evidence that Cep70 is a mediator of paclitaxel sensitivity in breast cancer. Cell proliferation assays show that Cep70 expression correlates with paclitaxel sensitivity in breast cancer cell lines. In addition, paclitaxel sensitivity varies when altering Cep70 expression level. Mechanistic studies reveal that Cep70 interacts with tubulin, and promotes the ability of paclitaxel to stimulate microtubule assembly. These data demonstrate that Cep70 mediates paclitaxel sensitivity in breast cancer. Full article

(This article belongs to the Special Issue Microtubule-Targeting Agents)

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2 pages, 134 KiB

Open AccessReply

Reply to the Letter to the Editor by C. Nicolazzo et al.: “Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy”

by Angela Alama^*

, Simona Coco

, Irene Vanni and Francesco Grossi

Lung Cancer Unit, IRCCS AOU San Martino—IST Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova, Italy

Int. J. Mol. Sci. 2017, 18(6), 1309; https://doi.org/10.3390/ijms18061309 - 19 Jun 2017

Cited by 1 | Viewed by 3432

Abstract

Reply: Thank you for the valuable comments. We agree with the concern that distinguishing genuine circulating tumor cells (CTCs) from other circulating cells by morphology may be questionable.[...] Full article

2 pages, 166 KiB

Open AccessLetter

Letter to the Editor: “Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy”

by Chiara Nicolazzo

, Cristina Raimondi, Flavia Loreni, Paola Gazzaniga and Angela Gradilone^*

Circulating Tumor Cells Unit, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy

Int. J. Mol. Sci. 2017, 18(6), 1308; https://doi.org/10.3390/ijms18061308 - 19 Jun 2017

Viewed by 3550

Abstract

To the Editor, We read with great interest the article “Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy” published by Coco, S. et al. in International Journal [...] Read more.

To the Editor, We read with great interest the article “Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy” published by Coco, S. et al. in International Journal of Molecular Sciences on 11 May 2017 [1].[...] Full article

11 pages, 13186 KiB

Open AccessArticle

Candida albicans Impairments Induced by Peppermint and Clove Oils at Sub-Inhibitory Concentrations

by Katarzyna Rajkowska^1,*

, Anna Otlewska¹, Alina Kunicka-Styczyńska¹

and Agnieszka Krajewska²

¹ Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz 90-924, Poland

² Institute of General Food Chemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz 90-924, Poland

Int. J. Mol. Sci. 2017, 18(6), 1307; https://doi.org/10.3390/ijms18061307 - 19 Jun 2017

Cited by 26 | Viewed by 8734

Abstract

Members of Candida species cause significant health problems, inducing various types of superficial and deep-seated mycoses in humans. In order to prevent from Candida sp. development, essential oils are more and more frequently applied, due to their antifungal activity, low toxicity if used [...] Read more.

Members of Candida species cause significant health problems, inducing various types of superficial and deep-seated mycoses in humans. In order to prevent from Candida sp. development, essential oils are more and more frequently applied, due to their antifungal activity, low toxicity if used appropriately, and biodegrability. The aim of the study was to characterize the early alterations in Candida albicans metabolic properties in relation to proteins and chromosomal DNA profiles, after treatment with peppermint and clove oils at sub-inhibitory concentrations. The yeasts were affected by the oils even at a concentration of 0.0075% v/v, which resulted in changes in colony morphotypes and metabolic activities. Peppermint and clove oils at concentrations ranging from 0.015× MIC (minimal inhibitory concentration) to 0.5× MIC values substantially affected the enzymatic abilities of C. albicans, and these changes were primarily associated with the loss or decrease of activity of all 9 enzymes detected in the untreated yeast. Moreover, 29% isolates showed additional activity of N-acetyl-β-glucosaminidase and 14% isolates—α-fucosidase in comparison to the yeast grown without essential oils addition. In response to essential oils at 0.25–0.5× MIC, extensive changes in C. albicans whole-cell protein profiles were noted. However, the yeast biochemical profiles were intact with the sole exception of the isolate treated with clove oil at 0.5× MIC. The alterations were not attributed to gross chromosomal rearrangements in C. albicans karyotype. The predominantly observed decrease in protein fractions and the yeast enzymatic activity after treatment with the oils should be considered as a phenotypic response of C. albicans to the essential oils at their sub-inhibitory concentrations and may lead to the reduction of this yeast pathogenicity. Full article

(This article belongs to the Special Issue Effective Mechanisms of Plant Bioactive Essential Fats and Oils)

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10 pages, 643 KiB

Open AccessReview

Fortifying Horticultural Crops with Essential Amino Acids: A Review

by Guoping Wang¹, Mengyun Xu¹, Wenyi Wang^1,2,* and Gad Galili^2,*

¹ College of Horticulture, South China Agricultural University, Guangzhou 510642, China

² Department of Plant Science, Weizmann Institute of Science, Rehovot 76100, Israel

Int. J. Mol. Sci. 2017, 18(6), 1306; https://doi.org/10.3390/ijms18061306 - 19 Jun 2017

Cited by 36 | Viewed by 8316

Abstract

To feed the world′s growing population, increasing the yield of crops is not the only important factor, improving crop quality is also important, and it presents a significant challenge. Among the important crops, horticultural crops (particularly fruits and vegetables) provide numerous health compounds, [...] Read more.

To feed the world′s growing population, increasing the yield of crops is not the only important factor, improving crop quality is also important, and it presents a significant challenge. Among the important crops, horticultural crops (particularly fruits and vegetables) provide numerous health compounds, such as vitamins, antioxidants, and amino acids. Essential amino acids are those that cannot be produced by the organism and, therefore, must be obtained from diet, particularly from meat, eggs, and milk, as well as a variety of plants. Extensive efforts have been devoted to increasing the levels of essential amino acids in plants. Yet, these efforts have been met with very little success due to the limited genetic resources for plant breeding and because high essential amino acid content is generally accompanied by limited plant growth. With a deep understanding of the biosynthetic pathways of essential amino acids and their interactions with the regulatory networks in plants, it should be possible to use genetic engineering to improve the essential amino acid content of horticultural plants, rendering these plants more nutritionally favorable crops. In the present report, we describe the recent advances in the enhancement of essential amino acids in horticultural plants and possible future directions towards their bio-fortification. Full article

(This article belongs to the Section Molecular Plant Sciences)

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8 pages, 178 KiB

Open AccessReview

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

by Antonis Makrigiannakis^1,*,†, Thomas Vrekoussis^2,†, Emmanouel Zoumakis³, Sophia N. Kalantaridou⁴ and Udo Jeschke⁵

¹ Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion 71003, Greece

² Department of Obstetrics and Gynecology, Medical School, University of Ioannina, Ioannina 45110, Greece

³ Department of Pediatrics, Medical School, University of Athens, Athens 11527, Greece

⁴ Second Department of Obstetrics and Gynecology, Medical School, University of Athens, Athens 11528, Greece

⁵ Departments of Obstetrics and Gynecology, Medical School, Ludwig-Maximilians University of Munich, Campus Innenstadt & Campus Grosshadern, Munich 80337, Germany

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2017, 18(6), 1305; https://doi.org/10.3390/ijms18061305 - 19 Jun 2017

Cited by 55 | Viewed by 8817

Abstract

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, [...] Read more.

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. Full article

(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)

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Int. J. Mol. Sci., Volume 18, Issue 6 (June 2017) – 228 articles

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