Deyarina Gonzalez

Swansea University | SWAN · Centre for Nanohealth "CNH"

The mechanical homeostasis of tissues can be altered in response to trauma or disease, such as cancer, resulting in altered mechanotransduction pathways that have been shown to impact tumor development, progression, and the efficacy of therapeutic approaches. Specifically, ovarian cancer progression is parallel to an increase in tissue stiffness an...

Background Ovarian cancer (OC) is typically diagnosed late, associated with high rates of metastasis and the onset of ascites during late stage disease. Understanding the tumor microenvironment and how it impacts the efficacy of current treatments, including immunotherapies, needs effective in vivo models that are fully characterized. In particular...

Objectives To investigate whether women with overactive bladder (OAB) symptoms and no evidence of clinical infection by conventional clean-catch midstream urine cultures have alternative indicators of sub-clinical infection. Patients/Subjects, Materials & Methods The study was a prospective, blinded case-control study with 147 participants recruit...

Histone Deacetylase (HDAC) enzymes are upregulated in cancer leading to the development of HDAC inhibiting compounds, several of which are currently in clinical trials. Side effects associated with toxicity and non-specific targeting indicate the need for efficient drug delivery approaches and tumor specific targeting to enhance HDAC efficacy in so...

Extracellular vesicles (EVs) are studied extensively as natural biomolecular shuttles and for their diagnostic and therapeutic potential. This exponential rise in interest has highlighted the need for highly robust and reproducible approaches for EV characterisation. Here we optimise quantitative nanomechanical tools and demonstrate the advantages...

Endometrial cancer (EC) is the sixth most prevalent female cancer globally and although high rates of success are achieved when diagnosed at an early stage, the 5-year survival rate for cancers diagnosed at Stages II–IV is below 50%. Improving patient outcomes will necessitate the introduction of novel therapies to the clinic. Pan-cyclin-dependent...

Endometrial receptivity is mediated by adhesion molecules at the endometrium-trophoblast interface where osteopontin (OPN) and CD44 form a protein complex that plays an important role in embryo recognition. Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory pol...

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigen...

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigen...

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigen...

Bespoke nanoparticle systems can enhance drug delivery, preventing systemic exposure by modifying release kinetics and increasing tumour penetration. Flexible nano vector systems have led to selective tumour targeting through surface modifications and the addition of target moieties over expressed in the cancer microenvironment. As such nanomedicin...

High dose selenium acts as a cytotoxic agent, with potential applications in cancer treatment. However, clinical trials have failed to show any chemotherapeutic value of selenium at safe and tolerated doses (<90 μg/day). To enable the successful exploitation of selenium for cancer treatment, we evaluated inorganic selenium nanoparticles (SeNP), and...

In vitro fertilization (IVF) is the most common assisted reproductive technology used to treat infertility. Embryo selection for transfer in IVF cycles relies on the morphological evaluation by embryologists, either by conventional microscopic assessment or more recently by time-lapse imaging systems. Despite the introduction of time-lapse imaging...

A fundamental structural component of extracellular matrix in all connective and interstitial tissue, collagen is the most abundant protein in the human body. To date, mammalian collagens sources represent the golden standard for multiple biomedical applications, while marine-derived collagens have largely been used in industry (food, pharmaceutica...

Background: The treatment of endometrial cancer (EC), the most common gynecological cancer, is currently hampered by the toxicity of current cytotoxic agents, meaning novel therapeutic approaches are urgently required. Methods: A cohort of 161 patients was evaluated for the expression of the receptor for advanced glycation end products (RAGE) in...

Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, with a prevalence of up to 12% of women of reproductive age, and is in part characterised by elevated circulating androgens and aberrant expression of androgen receptor (AR) in the endometrium. A high percentage of PCOS patients suffer from infertility, a condition that appears t...

DNA methylation and histone deacetylation are key epigenetic processes involved in normal cellular function and tumorigenesis. Therapeutic strategies based on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors are currently in use and under development for the treatment of cancers. Genome-wide DNA methylation profiling has been...

Infections of the female reproductive tract are a major cause of morbidity and mortality in humans, requiring significant investment to sustain treatment and representing a major challenge to health. The increasing prevalence of bacterial resistance, and an almost complete absence of new antibiotic therapies for the past five decades, mean there is...

New approaches to treat ovarian cancer, the fifth leading cause of cancer mortality among women, are being sought, with the targeting of epigenetic modulators now receiving much attention. The histone acetyltransferase HBO1 functions in regulating diverse molecular processes, including DNA repair, transcription and replication, and is highly expres...

Antibodies, antibody-like molecules, and therapeutics incorporating antibodies as a targeting moiety, such as antibody-drug conjugates, offer significant potential for the development of highly efficacious drugs against a wide range of disorders. Despite some success, truly harnessing the superior targeting properties of these molecules requires a...

During decidualization, human mesenchymal-like endometrial stromal cells undergo well characterized cellular and molecular transformations in preparation for accepting a developing embryo. Modulation of cellular biophysical properties during decidualization is likely to be important in receptivity and support of the embryo in the uterus. Here we as...

Endometrial cancer has numerous established risk factors including excessive unopposed estrogen exposure, tamoxifen, obesity and polycystic ovary syndrome (PCOS). These risk factors may promote inflammation, an important hallmark of cancer. Since the endometrium is a site of regular and repeated inflammation during the menstrual cycle, the regulati...

Gynaecological cancers: malignancies of the cervix,uterus,ovaries,vagina and vulva,are responsible for over 1.1 million new cancer cases and almost half a million deaths annually. Ovarian cancer in particular is difficult to treat due to often being diagnosed at a late stage,and the incidence of uterine and vulvar malignancies are both on the rise....

Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and neg...

Human chorionic gonadotropin (hCG), a 37 kDa glycoprotein hormone, is a key diagnostic marker of pregnancy and has been cited as an important biomarker in relation to cancerous tumors found in the prostate, ovaries and bladder. A novel chemically-modified epitaxial graphene diagnostic sensor has been developed for ultrasensitive detection of the b...

Signals that disrupt β-catenin association to cadherins may influence the translocation of β-catenin to the nucleus to regulate transcription. Post-translational modification of proteins is a signalling event that may lead to changes in structural conformation, association or function of the target proteins. NO and its derivatives induce nitration...

Densitometric analysis of immunoblots shown in Figure 2. Protein bands were visualized using a ChemiDoc System Bio-Rad Imager (Bio-Rad) and quantified by Quantity One® Imaging software (Bio-Rad) as described in Methods. Results were expressed as Band Density normalised to α-tubulin and are expressed as Intensity per square millimetres (INT*mm2). St...

NO regulates the expression and function of VE-cadherin/p120catenin/β-catenin complex in H5V cells. Panel A. Expression of VE-cadherin, p120-catenin (p120-ctn) and β-catenin is reduced in HUVEC cells incubated with IFNγ/LPS. NOS inhibitor LNMMA attenuates NO effect on VE-cadherin/catenin complex. HUVEC TX fractions and total cell lysates were analy...

In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and i...

Endometrium of fertile women expresses progesterone-regulated Mucin 1 (MUC1) that carries selectin ligands recognized by the human blastocyst. Altered MUC1 expression at the time of implantation may contribute to endometrial infertility. The aim was to assess the expression of MUC1 in the endometrium from polycystic ovary syndrome (PCOS), endometri...

Atomic force microscopy enables the simultaneous acquisition of high-resolution topographical and biophysical data allowing integrated analysis of cell surfaces during development and pathogenesis, and, critically, can link molecular and biophysical events. Here we used atomic force microscopy to analyse endometrial epithelial cells and neuronally...

The formation of advanced glycation end-products (AGEs), also called the Maillard reaction, occurs ubiquitously and irreversibly in patients with diabetes mellitus and its consequences are especially relevant to many inflammatory events leading to vascular dysfunctions and organ injury. The present review intends to highlight some relevant aspects...

The eukaryotic SIN3 protein is the central component of the evolutionarily conserved multisubunit SIN3 complex that has roles in regulating gene expression and genome stability. Here we characterise the structure of the SIN3 protein in higher plants through the analysis of SNL1 (SIN3-LIKE1), SNL2, SNL3, SNL4, SNL5 and SNL6, a family of six SIN3 hom...

L-selectin ligands, localized to the luminal epithelium at the time of implantation, may support the early stages of blastocyst attachment. We have assessed the expression of two L-selectin ligands, defined by MECA-79 and HECA-452 monoclonal antibodies, and the sulfotransferase GlcNAc6ST-2, involved in generation of L-selectin ligand epitopes, in t...

Background information: The endometrial epithelial cell membrane is a key interface in female reproductive biology. Steroid hormones play a predominant role in cyclic changes which occur at this interface during the female menstrual cycle. Specific changes in the morphology of the endometrial epithelial cell surface become apparent with the epithe...

The endometrium is commonly infected with bacteria leading to severe disease of the uterus in cattle and humans. The endometrial epithelium is the first line of defence for this mucosal surface against bacteria and Toll-like receptors (TLRs) are a critical component of the innate immune system for detection of pathogen associated molecular patterns...

The in vitro antioxidant and free radical scavenging properties of a stem bark aqueous extract of mango tree (Mangifera indica L.), whose formulations are used in Cuba as food supplements under the brand name of Vimang�, were studied. Luminol-enhanced chemiluminescence was used to elucidate the effect of this extract on the generation of reactive o...

Transcription corepressors are general regulators controlling the expression of genes involved in multiple signaling pathways and developmental programs. Repression is mediated through mechanisms including the stabilization of a repressive chromatin structure over control regions and regulation of Mediator function inhibiting RNA polymerase II acti...

A standard aqueous extract of Mangifera indica L., used in Cuba as antioxidant under the brand name VIMANG, was tested in vivo for its anti-inflammatory activity, using commonly accepted assays. The standard extract of M. indica, administered orally (50-200mg/kg body wt.), reduced ear edema induced by arachidonic acid (AA) and phorbol myristate ace...

Iron regulatory protein-1 (IRP-1) is a bifunctional [4Fe-4S] protein that functions as a cytosolic aconitase or as a trans-regulatory factor controlling iron homeostasis at a post-transcriptional level. Because IRP-1 is a sensitive target protein for nitric oxide (NO), we investigated whether this protein is nitrated in inflammatory macrophages and...

Transcription repression plays important roles in preventing crucial regulatory proteins from being expressed in inappropriate temporal or spatial domains. LEUNIG (LUG) and SEUSS (SEU) normally act to prevent ectopic expression of the floral homeotic gene AGAMOUS in flowers. LUG encodes a protein with sequence similarities to the yeast Tup1 corepre...

A standard aqueous extract of Mangifera indica L., used in Cuba as an antioxidant under the brand name of VIMANG, was tested in vivo for its anti-inflammatory activity using commonly accepted assays. M. indica extract, administered topically (0.5-2 mg per ear), reduced ear edema induced by arachidonic acid (AA) and phorbol myristate acetate (PMA, E...

Vascular endothelial cadherin (VE-cadherin), which is localized at adherent junctions, is involved in the control of vascular permeability. A growing body of evidence indicates that NO modulates the movement of fluid and proteins out of the vasculature. In this paper, we investigated whether NO can disrupt the VE-cadherin complex. We found that tre...

Endothelial cell (EC) junctions regulate in large part the integrity and barrier function of the vascular endothelium. Advanced glycation end-products (AGEs), the irreversibly formed reactive derivatives of non-enzymic glucose-protein condensation reactions, are strongly implicated in endothelial dysfunction that distinguishes diabetes- and aging-a...

Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from elevated stress. To assess its possible analgesic and antiinflammatory effects, the results of a standard extract evaluation are presented. Analgesia was determined using acetic acid-induced abdominal constriction and formalin-ind...

We examined whether albumin-derived advanced glycosylation end products (AGEs) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic endothelial cells were observed when exposed to different concentrations of albumin-derived AGEs. Western and Northern blot ana...